Epithelial ovarian tumors genetics: Difference between revisions

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__NOTOC__


{{CMG}}{{AE}}{{HMHJ}}
{| class="wikitable"
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! colspan="3" style="background:#4479BA; color: #FFFFFF;" align="center" + |Possible genetic alteration in epithelial ovarian cancers
|-
!style="background:#4479BA; color: #FFFFFF;" align="center" + |Protein
!style="background:#4479BA; color: #FFFFFF;" align="center" + |Normal function
!style="background:#4479BA; color: #FFFFFF;" align="center" + |Function in malignancy
|-
|style="background:#DCDCDC;" align="center" + | Human Epidermal growth factor receptor (HER-1)<ref name="pmid28513565">{{cite journal |vauthors=Wee P, Wang Z |title=Epidermal Growth Factor Receptor Cell Proliferation Signaling Pathways |journal=Cancers (Basel) |volume=9 |issue=5 |pages= |date=May 2017 |pmid=28513565 |pmc=5447962 |doi=10.3390/cancers9050052 |url=}}</ref><ref name="pmid25276427">{{cite journal |vauthors=Iqbal N, Iqbal N |title=Human Epidermal Growth Factor Receptor 2 (HER2) in Cancers: Overexpression and Therapeutic Implications |journal=Mol Biol Int |volume=2014 |issue= |pages=852748 |date=2014 |pmid=25276427 |pmc=4170925 |doi=10.1155/2014/852748 |url=}}</ref>
|
* Promotes cell proliferation
* Opposes apoptosis
* Regulates differentiation
|
* Activating mutation
* Increased cellular proliferation
* Inhibition of apoptosis
|-
|style="background:#DCDCDC;" align="center" + |Human Epidermal Growth Factor Receptor 2 (HER-2)<ref name="pmid28513565">{{cite journal |vauthors=Wee P, Wang Z |title=Epidermal Growth Factor Receptor Cell Proliferation Signaling Pathways |journal=Cancers (Basel) |volume=9 |issue=5 |pages= |date=May 2017 |pmid=28513565 |pmc=5447962 |doi=10.3390/cancers9050052 |url=}}</ref><ref name="pmid25276427">{{cite journal |vauthors=Iqbal N, Iqbal N |title=Human Epidermal Growth Factor Receptor 2 (HER2) in Cancers: Overexpression and Therapeutic Implications |journal=Mol Biol Int |volume=2014 |issue= |pages=852748 |date=2014 |pmid=25276427 |pmc=4170925 |doi=10.1155/2014/852748 |url=}}</ref>
|
* Promotes cell prolifeartion
* Inhibition of apoptosis
* Regulates differentiation
|
* Activating mutation
* Increased cellular proliferation
* Inhibition of apoptosis
|-
|style="background:#DCDCDC;" align="center" + |Non-receptor tyrosine kinase Src<ref name="pmid21334414">{{cite journal |vauthors=Zan L, Wu H, Jiang J, Zhao S, Song Y, Teng G, Li H, Jia Y, Zhou M, Zhang X, Qi J, Wang J |title=Temporal profile of Src, SSeCKS, and angiogenic factors after focal cerebral ischemia: correlations with angiogenesis and cerebral edema |journal=Neurochem. Int. |volume=58 |issue=8 |pages=872–9 |date=July 2011 |pmid=21334414 |pmc=3100427 |doi=10.1016/j.neuint.2011.02.014 |url=}}</ref><ref name="pmid24481818">{{cite journal |vauthors=Reinecke JB, Katafiasz D, Naslavsky N, Caplan S |title=Regulation of Src trafficking and activation by the endocytic regulatory proteins MICAL-L1 and EHD1 |journal=J. Cell. Sci. |volume=127 |issue=Pt 8 |pages=1684–98 |date=April 2014 |pmid=24481818 |pmc=3986674 |doi=10.1242/jcs.133892 |url=}}</ref>
|Involved in regulation of
* Gene transcription
* Angiogenesis
* Cellular adhesion
* Cellular proliferation
|
* Activating mutation
* Increased angiogenesis
* Decreased cellular adhesion
* Increased tumor metastasis
* Increased cellular proliferation
|-
|style="background:#DCDCDC;" align="center" + |Colony stimulating factor-1/fms<ref name="pmid21761359">{{cite journal |vauthors=Saad AF, Hu W, Sood AK |title=Microenvironment and pathogenesis of epithelial ovarian cancer |journal=Horm Cancer |volume=1 |issue=6 |pages=277–90 |date=December 2010 |pmid=21761359 |pmc=3199131 |doi=10.1007/s12672-010-0054-2 |url=}}</ref><ref name="pmid28629162">{{cite journal |vauthors=Dwyer AR, Greenland EL, Pixley FJ |title=Promotion of Tumor Invasion by Tumor-Associated Macrophages: The Role of CSF-1-Activated Phosphatidylinositol 3 Kinase and Src Family Kinase Motility Signaling |journal=Cancers (Basel) |volume=9 |issue=6 |pages= |date=June 2017 |pmid=28629162 |pmc=5483887 |doi=10.3390/cancers9060068 |url=}}</ref><ref name="pmid19711348">{{cite journal |vauthors=Abraham D, Zins K, Sioud M, Lucas T, Schäfer R, Stanley ER, Aharinejad S |title=Stromal cell-derived CSF-1 blockade prolongs xenograft survival of CSF-1-negative neuroblastoma |journal=Int. J. Cancer |volume=126 |issue=6 |pages=1339–52 |date=March 2010 |pmid=19711348 |pmc=3222589 |doi=10.1002/ijc.24859 |url=}}</ref>
|
* Increased macrophage survival
* Increased macrophage proliferation
* Increased macrophage differentiation
|
* Activating mutation
* Stimulation of tumor cell proliferation
* Increased angiogenesis
* Promotes tumor invasion
* Increased metastasis
* Decreased anoikis
|-
|style="background:#DCDCDC;" align="center" + |Insulin-like growth factor/receptor ILGF/ILGFR<ref name="pmid11577173">{{cite journal |vauthors=Laron Z |title=Insulin-like growth factor 1 (IGF-1): a growth hormone |journal=MP, Mol. Pathol. |volume=54 |issue=5 |pages=311–6 |date=October 2001 |pmid=11577173 |pmc=1187088 |doi= |url=}}</ref><ref name="pmid22682634">{{cite journal |vauthors=Weroha SJ, Haluska P |title=The insulin-like growth factor system in cancer |journal=Endocrinol. Metab. Clin. North Am. |volume=41 |issue=2 |pages=335–50, vi |date=June 2012 |pmid=22682634 |pmc=3614012 |doi=10.1016/j.ecl.2012.04.014 |url=}}</ref><ref name="pmid12237896">{{cite journal |vauthors=Lukanova A, Lundin E, Toniolo P, Micheli A, Akhmedkhanov A, Rinaldi S, Muti P, Lenner P, Biessy C, Krogh V, Zeleniuch-Jacquotte A, Berrino F, Hallmans G, Riboli E, Kaaks R |title=Circulating levels of insulin-like growth factor-I and risk of ovarian cancer |journal=Int. J. Cancer |volume=101 |issue=6 |pages=549–54 |date=October 2002 |pmid=12237896 |doi=10.1002/ijc.10613 |url=}}</ref>
|
* Promotes growth
* Increased survival
|
* Activating mutation
* Increased proliferation
* Enhanced survival
* Suppression of cell cycle regulators
|-
|style="background:#DCDCDC;" align="center" + |k-ras<ref name="pmid22589270">{{cite journal |vauthors=Prior IA, Lewis PD, Mattos C |title=A comprehensive survey of Ras mutations in cancer |journal=Cancer Res. |volume=72 |issue=10 |pages=2457–67 |date=May 2012 |pmid=22589270 |pmc=3354961 |doi=10.1158/0008-5472.CAN-11-2612 |url=}}</ref><ref name="pmid20007845">{{cite journal |vauthors=Franklin WA, Haney J, Sugita M, Bemis L, Jimeno A, Messersmith WA |title=KRAS mutation: comparison of testing methods and tissue sampling techniques in colon cancer |journal=J Mol Diagn |volume=12 |issue=1 |pages=43–50 |date=January 2010 |pmid=20007845 |pmc=2797717 |doi=10.2353/jmoldx.2010.080131 |url=}}</ref>
|
* Cellular proliferation
* Cell survival
|
* Activating mutation
* Increased proliferation
* Enhanced survival
|-
|style="background:#DCDCDC;" align="center" + |b-raf<ref name="pmid18060073">{{cite journal |vauthors=Estep AL, Palmer C, McCormick F, Rauen KA |title=Mutation analysis of BRAF, MEK1 and MEK2 in 15 ovarian cancer cell lines: implications for therapy |journal=PLoS ONE |volume=2 |issue=12 |pages=e1279 |date=December 2007 |pmid=18060073 |pmc=2093994 |doi=10.1371/journal.pone.0001279 |url=}}</ref><ref name="pmid22930283">{{cite journal |vauthors=Grisham RN, Iyer G, Garg K, Delair D, Hyman DM, Zhou Q, Iasonos A, Berger MF, Dao F, Spriggs DR, Levine DA, Aghajanian C, Solit DB |title=BRAF mutation is associated with early stage disease and improved outcome in patients with low-grade serous ovarian cancer |journal=Cancer |volume=119 |issue=3 |pages=548–554 |date=February 2013 |pmid=22930283 |pmc=3961140 |doi=10.1002/cncr.27782 |url=}}</ref>
|
* Cellular proliferation
* Cellular differentiation
|
* Activating mutation
* Increased proliferation
* Enhanced growth
|-
|style="background:#DCDCDC;" align="center" + |Transforming growth factor-β<ref name="pmid28758950">{{cite journal |vauthors=Alsina-Sanchís E, Figueras A, Lahiguera A, Gil-Martín M, Pardo B, Piulats JM, Martí L, Ponce J, Matias-Guiu X, Vidal A, Villanueva A, Viñals F |title=TGFβ Controls Ovarian Cancer Cell Proliferation |journal=Int J Mol Sci |volume=18 |issue=8 |pages= |date=July 2017 |pmid=28758950 |pmc=5578048 |doi=10.3390/ijms18081658 |url=}}</ref><ref name="pmid24511106">{{cite journal |vauthors=Principe DR, Doll JA, Bauer J, Jung B, Munshi HG, Bartholin L, Pasche B, Lee C, Grippo PJ |title=TGF-β: duality of function between tumor prevention and carcinogenesis |journal=J. Natl. Cancer Inst. |volume=106 |issue=2 |pages=djt369 |date=February 2014 |pmid=24511106 |pmc=3952197 |doi=10.1093/jnci/djt369 |url=}}</ref><ref name="pmid20018551">{{cite journal |vauthors=Bierie B, Moses HL |title=Transforming growth factor beta (TGF-beta) and inflammation in cancer |journal=Cytokine Growth Factor Rev. |volume=21 |issue=1 |pages=49–59 |date=February 2010 |pmid=20018551 |pmc=2834863 |doi=10.1016/j.cytogfr.2009.11.008 |url=}}</ref>
|
* May function as a tumor suppressor and a promoter
* Promotes growth arrest
* Maintains cellular homeostasis
|
* Increased proliferation
* Decreased apoptosis
* Epithelial-to-mesenchymal transition
* Sustained angiogenesis
* Evasion of immune surveillance
* Metastasis
|-
|style="background:#DCDCDC;" align="center" + |myc<ref name="pmid23071356">{{cite journal |vauthors=Miller DM, Thomas SD, Islam A, Muench D, Sedoris K |title=c-Myc and cancer metabolism |journal=Clin. Cancer Res. |volume=18 |issue=20 |pages=5546–53 |date=October 2012 |pmid=23071356 |pmc=3505847 |doi=10.1158/1078-0432.CCR-12-0977 |url=}}</ref><ref name="pmid22464321">{{cite journal |vauthors=Dang CV |title=MYC on the path to cancer |journal=Cell |volume=149 |issue=1 |pages=22–35 |date=March 2012 |pmid=22464321 |pmc=3345192 |doi=10.1016/j.cell.2012.03.003 |url=}}</ref><ref name="pmid26889675">{{cite journal |vauthors=Aughey GN, Grice SJ, Liu JL |title=The Interplay between Myc and CTP Synthase in Drosophila |journal=PLoS Genet. |volume=12 |issue=2 |pages=e1005867 |date=February 2016 |pmid=26889675 |pmc=4759343 |doi=10.1371/journal.pgen.1005867 |url=}}</ref>
|
* Derives cellular proliferation
* Increased growth
* Cell-cycle mediator
* Inhibits apoptosis
* Stem-cell renewal
|
* Activating mutation
* Increased proliferation
* Decreased apoptosis
* Increased metabolism in tumor cells
|-
|style="background:#DCDCDC;" align="center" + |Cyclin D/Cdk4/6<ref name="pmid12802071">{{cite journal |vauthors=Neumeister P, Pixley FJ, Xiong Y, Xie H, Wu K, Ashton A, Cammer M, Chan A, Symons M, Stanley ER, Pestell RG |title=Cyclin D1 governs adhesion and motility of macrophages |journal=Mol. Biol. Cell |volume=14 |issue=5 |pages=2005–15 |date=May 2003 |pmid=12802071 |pmc=165093 |doi=10.1091/mbc.02-07-0102 |url=}}</ref><ref name="pmid29309421">{{cite journal |vauthors=Dong P, Zhang C, Parker BT, You L, Mathey-Prevot B |title=Cyclin D/CDK4/6 activity controls G1 length in mammalian cells |journal=PLoS ONE |volume=13 |issue=1 |pages=e0185637 |date=2018 |pmid=29309421 |pmc=5757913 |doi=10.1371/journal.pone.0185637 |url=}}</ref><ref name="pmid8633069">{{cite journal |vauthors=Khleif SN, DeGregori J, Yee CL, Otterson GA, Kaye FJ, Nevins JR, Howley PM |title=Inhibition of cyclin D-CDK4/CDK6 activity is associated with an E2F-mediated induction of cyclin kinase inhibitor activity |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=93 |issue=9 |pages=4350–4 |date=April 1996 |pmid=8633069 |pmc=39540 |doi= |url=}}</ref>
|
* Cell-cycle mediator
* Controls G1 length
|
* Activating mutation
* Decreased G1 length
* Increased proliferation
* Increased angiogenesis
|-
|style="background:#DCDCDC;" align="center" + |Cyclin E/Cdk2<ref name="pmid15660127">{{cite journal |vauthors=Honda R, Lowe ED, Dubinina E, Skamnaki V, Cook A, Brown NR, Johnson LN |title=The structure of cyclin E1/CDK2: implications for CDK2 activation and CDK2-independent roles |journal=EMBO J. |volume=24 |issue=3 |pages=452–63 |date=February 2005 |pmid=15660127 |pmc=548659 |doi=10.1038/sj.emboj.7600554 |url=}}</ref><ref name="pmid26219338">{{cite journal |vauthors=Choudhary GS, Tat TT, Misra S, Hill BT, Smith MR, Almasan A, Mazumder S |title=Cyclin E/Cdk2-dependent phosphorylation of Mcl-1 determines its stability and cellular sensitivity to BH3 mimetics |journal=Oncotarget |volume=6 |issue=19 |pages=16912–25 |date=July 2015 |pmid=26219338 |pmc=4627281 |doi=10.18632/oncotarget.4857 |url=}}</ref><ref name="pmid8861947">{{cite journal |vauthors=Won KA, Reed SI |title=Activation of cyclin E/CDK2 is coupled to site-specific autophosphorylation and ubiquitin-dependent degradation of cyclin E |journal=EMBO J. |volume=15 |issue=16 |pages=4182–93 |date=August 1996 |pmid=8861947 |pmc=452142 |doi= |url=}}</ref>
|
* Cellular proliferation
* Cell-cycle mediator
* Assembly of the pre-replication complex
* Promotes G0 to cell cycle entry
* Promotes G1 to S phase transition
* Decreased apoptosis
|
* Activating mutation
* Increased cellular proliferation
* Impaired apoptosis
* Increased cellular survival
|-
|style="background:#DCDCDC;" align="center" + |Cyclin B/Cdk1<ref name="pmid28489780">{{cite journal |vauthors=Sun X, Zhangyuan G, Shi L, Wang Y, Sun B, Ding Q |title=Prognostic and clinicopathological significance of cyclin B expression in patients with breast cancer: A meta-analysis |journal=Medicine (Baltimore) |volume=96 |issue=19 |pages=e6860 |date=May 2017 |pmid=28489780 |pmc=5428614 |doi=10.1097/MD.0000000000006860 |url=}}</ref><ref name="pmid24324638">{{cite journal |vauthors=Huang Y, Sramkoski RM, Jacobberger JW |title=The kinetics of G2 and M transitions regulated by B cyclins |journal=PLoS ONE |volume=8 |issue=12 |pages=e80861 |date=2013 |pmid=24324638 |pmc=3851588 |doi=10.1371/journal.pone.0080861 |url=}}</ref><ref name="pmid17472438">{{cite journal |vauthors=Lindqvist A, van Zon W, Karlsson Rosenthal C, Wolthuis RM |title=Cyclin B1-Cdk1 activation continues after centrosome separation to control mitotic progression |journal=PLoS Biol. |volume=5 |issue=5 |pages=e123 |date=May 2007 |pmid=17472438 |pmc=1858714 |doi=10.1371/journal.pbio.0050123 |url=}}</ref>
|
* Cell-cycle mediator
* promotes G2 to M phase transition
|
* Activating mutation
* Increased cellular proliferation
* Promotes malignant transformation
|-
|style="background:#DCDCDC;" align="center" + |p16<ref name="pmid27572321">{{cite journal |vauthors=Yoon N, Yoon G, Park CK, Kim HS |title=Stromal p16 expression is significantly increased in malignant ovarian neoplasms |journal=Oncotarget |volume=7 |issue=40 |pages=64665–64673 |date=October 2016 |pmid=27572321 |pmc=5323106 |doi=10.18632/oncotarget.11660 |url=}}</ref><ref name="pmid9846965">{{cite journal |vauthors=Sano T, Oyama T, Kashiwabara K, Fukuda T, Nakajima T |title=Expression status of p16 protein is associated with human papillomavirus oncogenic potential in cervical and genital lesions |journal=Am. J. Pathol. |volume=153 |issue=6 |pages=1741–8 |date=December 1998 |pmid=9846965 |pmc=1866324 |doi=10.1016/S0002-9440(10)65689-1 |url=}}</ref><ref name="pmid25709969">{{cite journal |vauthors=Felix AS, Sherman ME, Hewitt SM, Gunja MZ, Yang HP, Cora RL, Boudreau V, Ylaya K, Lissowska J, Brinton LA, Wentzensen N |title=Cell-cycle protein expression in a population-based study of ovarian and endometrial cancers |journal=Front Oncol |volume=5 |issue= |pages=25 |date=2015 |pmid=25709969 |pmc=4321403 |doi=10.3389/fonc.2015.00025 |url=}}</ref>
|
* Member of the INK4 family of CDK inhibitors
* Inhibits Cyclin D/Cdk4/6
* Decreased G1 to S phase transition
|
* Lost or downregulated
* Decreased G1 length
* Increased proliferation
* Increased angiogenesis
|-
|style="background:#DCDCDC;" align="center" + |p27 (kip-1)<ref name="pmid19887899">{{cite journal |vauthors=Lee J, Kim SS |title=The function of p27 KIP1 during tumor development |journal=Exp. Mol. Med. |volume=41 |issue=11 |pages=765–71 |date=November 2009 |pmid=19887899 |pmc=2788730 |doi=10.3858/emm.2009.41.11.102 |url=}}</ref><ref name="pmid18583941">{{cite journal |vauthors=Roy S, Singh RP, Agarwal C, Siriwardana S, Sclafani R, Agarwal R |title=Downregulation of both p21/Cip1 and p27/Kip1 produces a more aggressive prostate cancer phenotype |journal=Cell Cycle |volume=7 |issue=12 |pages=1828–35 |date=June 2008 |pmid=18583941 |pmc=2744498 |doi=10.4161/cc.7.12.6024 |url=}}</ref><ref name="pmid11438653">{{cite journal |vauthors=Miskimins WK, Wang G, Hawkinson M, Miskimins R |title=Control of cyclin-dependent kinase inhibitor p27 expression by cap-independent translation |journal=Mol. Cell. Biol. |volume=21 |issue=15 |pages=4960–7 |date=August 2001 |pmid=11438653 |pmc=87223 |doi=10.1128/MCB.21.15.4960-4967.2001 |url=}}</ref>
|
* Inhibitor of Cyclin E/Cdk2
* Mediates cell cycle arrest
* Decreased G1 to S phase transition
* May act as oncogen and promote proliferation
|
* Lost or dysregulated
* Increase in cell proliferation
* Impaired apoptosis
|-
|style="background:#DCDCDC;" align="center" + |p21 (WAF-1)<ref name="pmid19440234">{{cite journal |vauthors=Abbas T, Dutta A |title=p21 in cancer: intricate networks  and multiple activities |journal=Nat. Rev. Cancer |volume=9 |issue=6 |pages=400–14 |date=June 2009 |pmid=19440234 |pmc=2722839 |doi=10.1038/nrc2657 |url=}}</ref><ref name="pmid15798220">{{cite journal |vauthors=Dash BC, El-Deiry WS |title=Phosphorylation of p21 in G2/M promotes cyclin B-Cdc2 kinase activity |journal=Mol. Cell. Biol. |volume=25 |issue=8 |pages=3364–87 |date=April 2005 |pmid=15798220 |pmc=1069593 |doi=10.1128/MCB.25.8.3364-3387.2005 |url=}}</ref><ref name="pmid8912526">{{cite journal |vauthors=Shi Y, Zou M, Farid NR, al-Sedairy ST |title=Evidence of gene deletion of p21 (WAF1/CIP1), a cyclin-dependent protein kinase inhibitor, in thyroid carcinomas |journal=Br. J. Cancer |volume=74 |issue=9 |pages=1336–41 |date=November 1996 |pmid=8912526 |pmc=2074763 |doi= |url=}}</ref>
|
* Inhibits cyclin-dependant kinases
* Cell-cycle arrest
* Decreased proliferation
* Promotes cellular differentiation
* May inhibit/promote apoptosis
* May act as oncogen and promote proliferation
|
* Lost or dysregulated
* Increase in cell proliferation
* Decreased cellular differentiation
* Decreased apoptosis
* Correlates positively
** tumour grade
** invasiveness
** aggressiveness
|-
|style="background:#DCDCDC;" align="center" + |Nuclear factor-κB<ref name="pmid20457564">{{cite journal |vauthors=Lawrence T |title=The nuclear factor NF-kappaB pathway in inflammation |journal=Cold Spring Harb Perspect Biol |volume=1 |issue=6 |pages=a001651 |date=December 2009 |pmid=20457564 |pmc=2882124 |doi=10.1101/cshperspect.a001651 |url=}}</ref><ref name="pmid21339307">{{cite journal |vauthors=Yang G, Xiao X, Rosen DG, Cheng X, Wu X, Chang B, Liu G, Xue F, Mercado-Uribe I, Chiao P, Du X, Liu J |title=The biphasic role of NF-kappaB in progression and chemoresistance of ovarian cancer |journal=Clin. Cancer Res. |volume=17 |issue=8 |pages=2181–94 |date=April 2011 |pmid=21339307 |pmc=3152795 |doi=10.1158/1078-0432.CCR-10-3265 |url=}}</ref><ref name="pmid24272484">{{cite journal |vauthors=Charbonneau B, Block MS, Bamlet WR, Vierkant RA, Kalli KR, Fogarty Z, Rider DN, Sellers TA, Tworoger SS, Poole E, Risch HA, Salvesen HB, Kiemeney LA, Baglietto L, Giles GG, Severi G, Trabert B, Wentzensen N, Chenevix-Trench G, Whittemore AS, Sieh W, Chang-Claude J, Bandera EV, Orlow I, Terry K, Goodman MT, Thompson PJ, Cook LS, Rossing MA, Ness RB, Narod SA, Kupryjanczyk J, Lu K, Butzow R, Dörk T, Pejovic T, Campbell I, Le ND, Bunker CH, Bogdanova N, Runnebaum IB, Eccles D, Paul J, Wu AH, Gayther SA, Hogdall E, Heitz F, Kaye SB, Karlan BY, Anton-Culver H, Gronwald J, Hogdall CK, Lambrechts D, Fasching PA, Menon U, Schildkraut J, Pearce CL, Levine DA, Kjaer SK, Cramer D, Flanagan JM, Phelan CM, Brown R, Massuger LF, Song H, Doherty JA, Krakstad C, Liang D, Odunsi K, Berchuck A, Jensen A, Lubinski J, Nevanlinna H, Bean YT, Lurie G, Ziogas A, Walsh C, Despierre E, Brinton L, Hein A, Rudolph A, Dansonka-Mieszkowska A, Olson SH, Harter P, Tyrer J, Vitonis AF, Brooks-Wilson A, Aben KK, Pike MC, Ramus SJ, Wik E, Cybulski C, Lin J, Sucheston L, Edwards R, McGuire V, Lester J, du Bois A, Lundvall L, Wang-Gohrke S, Szafron LM, Lambrechts S, Yang H, Beckmann MW, Pelttari LM, Van Altena AM, van den Berg D, Halle MK, Gentry-Maharaj A, Schwaab I, Chandran U, Menkiszak J, Ekici AB, Wilkens LR, Leminen A, Modugno F, Friel G, Rothstein JH, Vergote I, Garcia-Closas M, Hildebrandt MA, Sobiczewski P, Kelemen LE, Pharoah PD, Moysich K, Knutson KL, Cunningham JM, Fridley BL, Goode EL |title=Risk of ovarian cancer and the NF-κB pathway: genetic association with IL1A and TNFSF10 |journal=Cancer Res. |volume=74 |issue=3 |pages=852–61 |date=February 2014 |pmid=24272484 |pmc=3946482 |doi=10.1158/0008-5472.CAN-13-1051 |url=}}</ref>
|
* A transcription factor involved in regulation of
** immune response to inflammation
** expression of cytokines, chemokines, and adhesion molecules
** cell cycle
** apoptosis
* May function as a tumor suppressor and a promoter
|
* Dysregulated
* Increased angiogenesis
* Enhanced tumor growth
* Induces resistance to chemotherapy by acting as anti-apoptosis
|-
|style="background:#DCDCDC;" align="center" + |NOEY(ARHI)<ref name="pmid21643014">{{cite journal |vauthors=Badgwell DB, Lu Z, Le K, Gao F, Yang M, Suh GK, Bao JJ, Das P, Andreeff M, Chen W, Yu Y, Ahmed AA, S-L Liao W, Bast RC |title=The tumor-suppressor gene ARHI (DIRAS3) suppresses ovarian cancer cell migration through inhibition of the Stat3 and FAK/Rho signaling pathways |journal=Oncogene |volume=31 |issue=1 |pages=68–79 |date=January 2012 |pmid=21643014 |pmc=3170676 |doi=10.1038/onc.2011.213 |url=}}</ref><ref name="pmid9874798">{{cite journal |vauthors=Yu Y, Xu F, Peng H, Fang X, Zhao S, Li Y, Cuevas B, Kuo WL, Gray JW, Siciliano M, Mills GB, Bast RC |title=NOEY2 (ARHI), an imprinted putative tumor suppressor gene in ovarian and breast carcinomas |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=96 |issue=1 |pages=214–9 |date=January 1999 |pmid=9874798 |pmc=15119 |doi= |url=}}</ref><ref name="pmid7559524">{{cite journal |vauthors=Albanese C, Johnson J, Watanabe G, Eklund N, Vu D, Arnold A, Pestell RG |title=Transforming p21ras mutants and c-Ets-2 activate the cyclin D1 promoter through distinguishable regions |journal=J. Biol. Chem. |volume=270 |issue=40 |pages=23589–97 |date=October 1995 |pmid=7559524 |doi= |url=}}</ref><ref name="pmid23591839">{{cite journal |vauthors=Dobbin ZC, Landen CN |title=The importance of the PI3K/AKT/MTOR pathway in the progression of ovarian cancer |journal=Int J Mol Sci |volume=14 |issue=4 |pages=8213–27 |date=April 2013 |pmid=23591839 |pmc=3645739 |doi=10.3390/ijms14048213 |url=}}</ref>
|
* Inhibits cell growth
* Induces apoptosis
* Inhibits tumor cells migration through chemotaxis and haptotaxis
|
* Inactivating mutation
* Enhanced tumor growth
* Decreased apoptosis
* Increased chances for metastasis
|-
|style="background:#DCDCDC;" align="center" + |PIP3/Akt<ref name="pmid22952397">{{cite journal |vauthors=Hemmings BA, Restuccia DF |title=PI3K-PKB/Akt pathway |journal=Cold Spring Harb Perspect Biol |volume=4 |issue=9 |pages=a011189 |date=September 2012 |pmid=22952397 |pmc=3428770 |doi=10.1101/cshperspect.a011189 |url=}}</ref><ref name="pmid30334567">{{cite journal |vauthors=Nitulescu GM, Van De Venter M, Nitulescu G, Ungurianu A, Juzenas P, Peng Q, Olaru OT, Grădinaru D, Tsatsakis A, Tsoukalas D, Spandidos DA, Margina D |title=The Akt pathway in oncology therapy and beyond (Review) |journal=Int. J. Oncol. |volume=53 |issue=6 |pages=2319–2331 |date=December 2018 |pmid=30334567 |pmc=6203150 |doi=10.3892/ijo.2018.4597 |url=}}</ref>
|
* Akt is activated by PIP3 and plays a role in
** regulation of cellular growth
** cell cycle progression
** regulation of glucose metabolism
** genome stability
** gene transcription
** protein synthesis
** neovascularization
** promotes cell survival by blocking apoptosis
|
* Activating mutations
* Increased cellular proliferation
* Increased tumor cells survival
* Increased tumor cells migration
* Increased tumor cells invasion
* Chemotherapy resistance
* Decreased apoptosis
* May promote angiogenesis
|-
|style="background:#DCDCDC;" align="center" + |PTEN<ref name="pmid23223894">{{cite journal |vauthors=Shi Y, Paluch BE, Wang X, Jiang X |title=PTEN at a glance |journal=J. Cell. Sci. |volume=125 |issue=Pt 20 |pages=4687–92 |date=October 2012 |pmid=23223894 |pmc=3517091 |doi=10.1242/jcs.093765 |url=}}</ref><ref name="pmid24170201">{{cite journal |vauthors=Tanwar PS, Mohapatra G, Chiang S, Engler DA, Zhang L, Kaneko-Tarui T, Ohguchi Y, Birrer MJ, Teixeira JM |title=Loss of LKB1 and PTEN tumor suppressor genes in the ovarian surface epithelium induces papillary serous ovarian cancer |journal=Carcinogenesis |volume=35 |issue=3 |pages=546–53 |date=March 2014 |pmid=24170201 |pmc=3941742 |doi=10.1093/carcin/bgt357 |url=}}</ref><ref name="pmid25361917">{{cite journal |vauthors=Hopkins BD, Parsons RE |title=Molecular pathways: intercellular PTEN and the potential of PTEN restoration therapy |journal=Clin. Cancer Res. |volume=20 |issue=21 |pages=5379–83 |date=November 2014 |pmid=25361917 |pmc=4362520 |doi=10.1158/1078-0432.CCR-13-2661 |url=}}</ref>
|
* Suppresses Akt and thus regulates cell cycle, cellular growth and apoptosis
* Regulates self-renewal and differentiation of human stem cells
* Regulates oocyte growth and follicular activation
* Regulates chemotaxis of neutrophils
* Inhibit cell invasion and migration
|
* Deletion or inactivating mutation
* Increased cellular proliferation
* Increased tumor cells survival
* Increased tumor cells migration
* Increased tumor cells invasion
* Decreased apoptosis
|-
|style="background:#DCDCDC;" align="center" + |p53<ref name="pmid20066118">{{cite journal |vauthors=Zilfou JT, Lowe SW |title=Tumor suppressive functions of p53 |journal=Cold Spring Harb Perspect Biol |volume=1 |issue=5 |pages=a001883 |date=November 2009 |pmid=20066118 |pmc=2773645 |doi=10.1101/cshperspect.a001883 |url=}}</ref><ref name="pmid24212651">{{cite journal |vauthors=Ozaki T, Nakagawara A |title=Role of p53 in Cell Death and Human Cancers |journal=Cancers (Basel) |volume=3 |issue=1 |pages=994–1013 |date=March 2011 |pmid=24212651 |pmc=3756401 |doi=10.3390/cancers3010994 |url=}}</ref><ref name="pmid30613473">{{cite journal |vauthors=Zhang Y, Cao L, Nguyen D, Lu H |title=TP53 mutations in epithelial ovarian cancer |journal=Transl Cancer Res |volume=5 |issue=6 |pages=650–663 |date=December 2016 |pmid=30613473 |pmc=6320227 |doi=10.21037/tcr.2016.08.40 |url=}}</ref>
|
* A transcription factor that
** regulates cell cycle
** promotes DNA damage repair
** promotes apoptosis
** maintains genomic integrity
|
* Loss results in
** DNA damage and carcinogenesis
** increased tumor cell growth and survival
** increased metastasis
** decreased apoptosis
** resistance to chemotherapy
|-
|style="background:#DCDCDC;" align="center" + |BRCA1<ref name="pmid22193408">{{cite journal |vauthors=Roy R, Chun J, Powell SN |title=BRCA1 and BRCA2: different roles in a common pathway of genome protection |journal=Nat. Rev. Cancer |volume=12 |issue=1 |pages=68–78 |date=December 2011 |pmid=22193408 |pmc=4972490 |doi=10.1038/nrc3181 |url=}}</ref><ref name="pmid28794804">{{cite journal |vauthors=Neff RT, Senter L, Salani R |title=BRCA mutation in ovarian cancer: testing, implications and treatment considerations |journal=Ther Adv Med Oncol |volume=9 |issue=8 |pages=519–531 |date=August 2017 |pmid=28794804 |pmc=5524247 |doi=10.1177/1758834017714993 |url=}}</ref><ref name="pmid16484695">{{cite journal |vauthors=Chen S, Iversen ES, Friebel T, Finkelstein D, Weber BL, Eisen A, Peterson LE, Schildkraut JM, Isaacs C, Peshkin BN, Corio C, Leondaridis L, Tomlinson G, Dutson D, Kerber R, Amos CI, Strong LC, Berry DA, Euhus DM, Parmigiani G |title=Characterization of BRCA1 and BRCA2 mutations in a large United States sample |journal=J. Clin. Oncol. |volume=24 |issue=6 |pages=863–71 |date=February 2006 |pmid=16484695 |pmc=2323978 |doi=10.1200/JCO.2005.03.6772 |url=}}</ref>
|
* A tumor suppressor that mediates double stranded DNA repair through
** homologous recombination pathway
** non-homologous end joining pathway
* Activates checkpoints in cell cycle
* Maintains genomic integrity
|
* Mutations are responsible for hereditary breast & ovarian tumors
* Loss results in
** DNA damage and carcinogenesis
** increased tumor cell growth and survival
|-
|style="background:#DCDCDC;" align="center" + |BRCA2<ref name="pmid22193408">{{cite journal |vauthors=Roy R, Chun J, Powell SN |title=BRCA1 and BRCA2: different roles in a common pathway of genome protection |journal=Nat. Rev. Cancer |volume=12 |issue=1 |pages=68–78 |date=December 2011 |pmid=22193408 |pmc=4972490 |doi=10.1038/nrc3181 |url=}}</ref><ref name="pmid28794804">{{cite journal |vauthors=Neff RT, Senter L, Salani R |title=BRCA mutation in ovarian cancer: testing, implications and treatment considerations |journal=Ther Adv Med Oncol |volume=9 |issue=8 |pages=519–531 |date=August 2017 |pmid=28794804 |pmc=5524247 |doi=10.1177/1758834017714993 |url=}}</ref><ref name="pmid16484695">{{cite journal |vauthors=Chen S, Iversen ES, Friebel T, Finkelstein D, Weber BL, Eisen A, Peterson LE, Schildkraut JM, Isaacs C, Peshkin BN, Corio C, Leondaridis L, Tomlinson G, Dutson D, Kerber R, Amos CI, Strong LC, Berry DA, Euhus DM, Parmigiani G |title=Characterization of BRCA1 and BRCA2 mutations in a large United States sample |journal=J. Clin. Oncol. |volume=24 |issue=6 |pages=863–71 |date=February 2006 |pmid=16484695 |pmc=2323978 |doi=10.1200/JCO.2005.03.6772 |url=}}</ref>
|
* A tumor suppressor that mediates double stranded DNA repair through
** homologous recombination pathway
* Maintains genomic integrity
* Protects replication fork and replication fidelity
|
* Mutations are responsible for hereditary breast & ovarian tumors
* Loss results in
** DNA damage and carcinogenesis
** increased tumor cell growth and survival
* Defects in maintenance the length of the nascent strand of DNA
|-
|style="background:#DCDCDC;" align="center" + |MLH1/MSH2<ref name="pmid24484585">{{cite journal |vauthors=Vymetalkova VP, Slyskova J, Korenkova V, Bielik L, Langerova L, Prochazka P, Rejhova A, Schwarzova L, Pardini B, Naccarati A, Vodicka P |title=Molecular characteristics of mismatch repair genes in sporadic colorectal tumors in Czech patients |journal=BMC Med. Genet. |volume=15 |issue= |pages=17 |date=January 2014 |pmid=24484585 |pmc=3913626 |doi=10.1186/1471-2350-15-17 |url=}}</ref><ref name="pmid21140452">{{cite journal |vauthors=Murphy MA, Wentzensen N |title=Frequency of mismatch repair deficiency in ovarian cancer: a systematic review This article is a US Government work and, as such, is in the public domain of the United States of America |journal=Int. J. Cancer |volume=129 |issue=8 |pages=1914–22 |date=October 2011 |pmid=21140452 |pmc=3107885 |doi=10.1002/ijc.25835 |url=}}</ref><ref name="pmid26710976">{{cite journal |vauthors=Heinen CD |title=Mismatch repair defects and Lynch syndrome: The role of the basic scientist in the battle against cancer |journal=DNA Repair (Amst.) |volume=38 |issue= |pages=127–34 |date=February 2016 |pmid=26710976 |pmc=4740212 |doi=10.1016/j.dnarep.2015.11.025 |url=}}</ref>
|
* Tumor suppressors that
* mediates DNA damage repair
* maintains genomic integrity
* possible regulation of cell cycle
|
* Loss results in
** DNA damage and carcinogenesis
** increased survival
** resistance to chemotherapy
** chromosomal instability
** microsatellite instability (MSI)
** the cytosine phosphate guanine (CpG) island methylator phenotype (CIMP)
|-
|style="background:#DCDCDC;" align="center" + |Fas ligand<ref name="pmid25656654">{{cite journal |vauthors=Peter ME, Hadji A, Murmann AE, Brockway S, Putzbach W, Pattanayak A, Ceppi P |title=The role of CD95 and CD95 ligand in cancer |journal=Cell Death Differ. |volume=22 |issue=4 |pages=549–59 |date=April 2015 |pmid=25656654 |pmc=4356349 |doi=10.1038/cdd.2015.3 |url=}}</ref><ref name="pmid14609433">{{cite journal |vauthors=Fraser M, Leung B, Jahani-Asl A, Yan X, Thompson WE, Tsang BK |title=Chemoresistance in human ovarian cancer: the role of apoptotic regulators |journal=Reprod. Biol. Endocrinol. |volume=1 |issue= |pages=66 |date=October 2003 |pmid=14609433 |pmc=270001 |doi=10.1186/1477-7827-1-66 |url=}}</ref><ref name="pmid7520535">{{cite journal |vauthors=Lowin B, Hahne M, Mattmann C, Tschopp J |title=Cytolytic T-cell cytotoxicity is mediated through perforin and Fas lytic pathways |journal=Nature |volume=370 |issue=6491 |pages=650–2 |date=August 1994 |pmid=7520535 |doi=10.1038/370650a0 |url=}}</ref>
|
* Binds to Fas receptor and induces apoptosis
* Expressed mainly on T-lymphocytes
* May induce apoptosis in cancer cells and virus infected cells
* May also be involved in
** liver regeneration following partial hepatectomy
** neurite outgrowth
|
* Most tumor cells are resistant to Fas-FasL mediated apoptosis
* Tumor cells express FasL to induce apoptosis in cytotoxic lymphocytes
* Promotes tumor cells survival
* Enhances tumor cells invasion
* Increased tumor cells migration
|-
|style="background:#DCDCDC;" align="center" + |Human leukocyte antigen-G<ref name="pmid27652273">{{cite journal |vauthors=Morandi F, Rizzo R, Fainardi E, Rouas-Freiss N, Pistoia V |title=Recent Advances in Our Understanding of HLA-G Biology: Lessons from a Wide Spectrum of Human Diseases |journal=J Immunol Res |volume=2016 |issue= |pages=4326495 |date=2016 |pmid=27652273 |pmc=5019910 |doi=10.1155/2016/4326495 |url=}}</ref><ref name="pmid26322846">{{cite journal |vauthors=Lin A, Yan WH |title=Human Leukocyte Antigen-G (HLA-G) Expression in Cancers: Roles in Immune Evasion, Metastasis and Target for Therapy |journal=Mol. Med. |volume=21 |issue=1 |pages=782–791 |date=November 2015 |pmid=26322846 |pmc=4749493 |doi=10.2119/molmed.2015.00083 |url=}}</ref><ref name="pmid17681474">{{cite journal |vauthors=Sheu JJ, Shih IeM |title=Clinical and biological significance of HLA-G expression in ovarian cancer |journal=Semin. Cancer Biol. |volume=17 |issue=6 |pages=436–43 |date=December 2007 |pmid=17681474 |pmc=2151836 |doi=10.1016/j.semcancer.2007.06.012 |url=}}</ref>
|
* Inhibits T-cell function through
** inhibiting proliferation
** causing cytotoxicity
** inducing apoptosis
** cytokine production in B lymphocytes
** inhibiting differentiation
* Inhibits proliferation and cytotoxicity of natural killer cells
* Promotes angiogenesis
* Inhibits chemotaxis
|
* Promotes progression of cancer through evasion of immune response by
** inhibiting T-cell functions by inducing apoptosis and decreased proliferation
** inhibiting T-cell differentiation through various mechanisms
* Inhibits proliferation and cytotoxicity of natural killer cells
* Promotes angiogenesis
* Inhibits chemotaxis of cytotoxic cells
|-
|style="background:#DCDCDC;" align="center" + |hTERT<ref name="pmid26823830">{{cite journal |vauthors=Lee YK, Chung HH, Kim JW, Song YS, Park NH |title=Expression of phosphorylated Akt and hTERT is associated with prognosis of epithelial ovarian carcinoma |journal=Int J Clin Exp Pathol |volume=8 |issue=11 |pages=14971–6 |date=2015 |pmid=26823830 |pmc=4713616 |doi= |url=}}</ref><ref name="pmid27548225">{{cite journal |vauthors=Ramlee MK, Wang J, Toh WX, Li S |title=Transcription Regulation of the Human Telomerase Reverse Transcriptase (hTERT) Gene |journal=Genes (Basel) |volume=7 |issue=8 |pages= |date=August 2016 |pmid=27548225 |pmc=4999838 |doi=10.3390/genes7080050 |url=}}</ref><ref name="pmid29526163">{{cite journal |vauthors=Leão R, Apolónio JD, Lee D, Figueiredo A, Tabori U, Castelo-Branco P |title=Mechanisms of human telomerase reverse transcriptase (hTERT) regulation: clinical impacts in cancer |journal=J. Biomed. Sci. |volume=25 |issue=1 |pages=22 |date=March 2018 |pmid=29526163 |pmc=5846307 |doi=10.1186/s12929-018-0422-8 |url=}}</ref>
|
* Maintains telomeres length
* Promotes replication
|
* Up-regulated in majority of human cancers
* Provides limitless replication ability to cancer cells
|-
|style="background:#DCDCDC;" align="center" + |Vascular endothelial growth factor/Vascular endothelial
growth factor receptor<ref name="pmid22101807">{{cite journal |vauthors=Masoumi Moghaddam S, Amini A, Morris DL, Pourgholami MH |title=Significance of vascular endothelial growth factor in growth and peritoneal dissemination of ovarian cancer |journal=Cancer Metastasis Rev. |volume=31 |issue=1-2 |pages=143–62 |date=June 2012 |pmid=22101807 |pmc=3350632 |doi=10.1007/s10555-011-9337-5 |url=}}</ref><ref name="pmid24263190">{{cite journal |vauthors=Goel HL, Mercurio AM |title=VEGF targets the tumour cell |journal=Nat. Rev. Cancer |volume=13 |issue=12 |pages=871–82 |date=December 2013 |pmid=24263190 |pmc=4011842 |doi=10.1038/nrc3627 |url=}}</ref><ref name="pmid10487612">{{cite journal |vauthors=Ohta Y, Shridhar V, Bright RK, Kalemkerian GP, Du W, Carbone M, Watanabe Y, Pass HI |title=VEGF and VEGF type C play an important role in angiogenesis and lymphangiogenesis in human malignant mesothelioma tumours |journal=Br. J. Cancer |volume=81 |issue=1 |pages=54–61 |date=September 1999 |pmid=10487612 |pmc=2374345 |doi=10.1038/sj.bjc.6690650 |url=}}</ref>
|
* Stimulates angiogenesis through
** increased endothelial cell survival
** Increased endothelial cell proliferation
** increased endothelial cell migration
* Increases vascular permeability
* May regulate fibroblasts in the stroma of tumors
* May effect tumor stem cells
|
* Promotes angiogenesis
* Promotes tumor cells growth
* May initiate carcinogenesis
* Promotes invasion and metastasis of tumor cells
|-
|style="background:#DCDCDC;" align="center" + |Interleukin-8<ref name="pmid27348007">{{cite journal |vauthors=David JM, Dominguez C, Hamilton DH, Palena C |title=The IL-8/IL-8R Axis: A Double Agent in Tumor Immune Resistance |journal=Vaccines (Basel) |volume=4 |issue=3 |pages= |date=June 2016 |pmid=27348007 |pmc=5041016 |doi=10.3390/vaccines4030022 |url=}}</ref><ref name="pmid29507619">{{cite journal |vauthors=Yung MM, Tang HW, Cai PC, Leung TH, Ngu SF, Chan KK, Xu D, Yang H, Ngan HY, Chan DW |title=GRO-α and IL-8 enhance ovarian cancer metastatic potential via the CXCR2-mediated TAK1/NFκB signaling cascade |journal=Theranostics |volume=8 |issue=5 |pages=1270–1285 |date=2018 |pmid=29507619 |pmc=5835935 |doi=10.7150/thno.22536 |url=}}</ref><ref name="pmid22015448">{{cite journal |vauthors=Escudero-Lourdes C, Wu T, Camarillo JM, Gandolfi AJ |title=Interleukin-8 (IL-8) over-production and autocrine cell activation are key factors in monomethylarsonous acid [MMA(III)]-induced malignant transformation of urothelial cells |journal=Toxicol. Appl. Pharmacol. |volume=258 |issue=1 |pages=10–8 |date=January 2012 |pmid=22015448 |pmc=3254786 |doi=10.1016/j.taap.2011.10.002 |url=}}</ref>
|
* Chemokine produced to recruit leukocytes and myeloid-derived suppressor cells
* Promotes epithelial-to-mesenchymal transition
* Promotes infection resolution
* Promotes angiogenesis
|
* Promotes epithelial-to-mesenchymal transition in tumor cells
* Promotes resistance to chemotherapy
* Tumor progression through immunosuppressive and pro-tumorigenic immune cells
* Promotes angiogenesis
* Promotes invasion and metastasis
|-
|style="background:#DCDCDC;" align="center" + |EphA2<ref name="pmid24705208">{{cite journal |vauthors=Park JE, Son AI, Zhou R |title=Roles of EphA2 in Development and Disease |journal=Genes (Basel) |volume=4 |issue=3 |pages=334–57 |date=July 2013 |pmid=24705208 |pmc=3924825 |doi=10.3390/genes4030334 |url=}}</ref><ref name="pmid26283684">{{cite journal |vauthors=Dunne PD, Dasgupta S, Blayney JK, McArt DG, Redmond KL, Weir JA, Bradley CA, Sasazuki T, Shirasawa S, Wang T, Srivastava S, Ong CW, Arthur K, Salto-Tellez M, Wilson RH, Johnston PG, Van Schaeybroeck S |title=EphA2 Expression Is a Key Driver of Migration and Invasion and a Poor Prognostic Marker in Colorectal Cancer |journal=Clin. Cancer Res. |volume=22 |issue=1 |pages=230–242 |date=January 2016 |pmid=26283684 |pmc=4694030 |doi=10.1158/1078-0432.CCR-15-0603 |url=}}</ref><ref name="pmid18443431">{{cite journal |vauthors=Lu C, Shahzad MM, Wang H, Landen CN, Kim SW, Allen J, Nick AM, Jennings N, Kinch MS, Bar-Eli M, Sood AK |title=EphA2 overexpression promotes ovarian cancer growth |journal=Cancer Biol. Ther. |volume=7 |issue=7 |pages=1098–103 |date=July 2008 |pmid=18443431 |pmc=2705979 |doi= |url=}}</ref>
|
* Promotes angiogenesis
* Plays a key role in development of
** Lens
** Inner ear
** Mammary glands
* Promotes kidney repair following injury
* Promotes bone remodeling bone remodeling
|
* Over-expressed in ovarian epithelial cancer
* Promotes tumor initiation
* Promotes neo-vascularization
* Promotes tumor invasion
* Promotes metastasis
|-
|style="background:#DCDCDC;" align="center" + |Matrix metalloproteinases<ref name="pmid17318226">{{cite journal |vauthors=Page-McCaw A, Ewald AJ, Werb Z |title=Matrix metalloproteinases and the regulation of tissue remodelling |journal=Nat. Rev. Mol. Cell Biol. |volume=8 |issue=3 |pages=221–33 |date=March 2007 |pmid=17318226 |pmc=2760082 |doi=10.1038/nrm2125 |url=}}</ref><ref name="pmid25945285">{{cite journal |vauthors=Caley MP, Martins VL, O'Toole EA |title=Metalloproteinases and Wound Healing |journal=Adv Wound Care (New Rochelle) |volume=4 |issue=4 |pages=225–234 |date=April 2015 |pmid=25945285 |pmc=4397992 |doi=10.1089/wound.2014.0581 |url=}}</ref><ref name="pmid25918438">{{cite journal |vauthors=Al-Alem L, Curry TE |title=Ovarian cancer: involvement of the matrix metalloproteinases |journal=Reproduction |volume=150 |issue=2 |pages=R55–64 |date=August 2015 |pmid=25918438 |pmc=4955511 |doi=10.1530/REP-14-0546 |url=}}</ref>
|
* Proteases that degrade tissues, matrix and other proteins and play a role in
** bone modeling and remodeling
** mammary development
** blood vessels remodeling
** a variety of other tissues such as tracheal tube
* Promotes inflammation through enzymatic activation
|
* Over-expressed in ovarian epithelial cancer
* Promotes tumor invasion through degradation of extra-cellular matrix
* Promotes metastasis through degradation of extra-cellular matrix
* May have a role in tumor initiation and angiogenesis
|-
|style="background:#DCDCDC;" align="center" + |αvβ3<ref name="pmid18998200">{{cite journal |vauthors=Cai WJ, Li MB, Wu X, Wu S, Zhu W, Chen D, Luo M, Eitenmüller I, Kampmann A, Schaper J, Schaper W |title=Activation of the integrins alpha 5beta 1 and alpha v beta 3 and focal adhesion kinase (FAK) during arteriogenesis |journal=Mol. Cell. Biochem. |volume=322 |issue=1-2 |pages=161–9 |date=February 2009 |pmid=18998200 |pmc=2758386 |doi=10.1007/s11010-008-9953-8 |url=}}</ref><ref name="pmid20628538">{{cite journal |vauthors=Liu Z, Wang F, Chen X |title=Integrin alpha(v)beta(3)-Targeted Cancer Therapy |journal=Drug Dev. Res. |volume=69 |issue=6 |pages=329–339 |date=2008 |pmid=20628538 |pmc=2901818 |doi=10.1002/ddr.20265 |url=}}</ref><ref name="pmid29548784">{{cite journal |vauthors=Shaw SK, Schreiber CL, Roland FM, Battles PM, Brennan SP, Padanilam SJ, Smith BD |title=High expression of integrin αvβ3 enables uptake of targeted fluorescent probes into ovarian cancer cells and tumors |journal=Bioorg. Med. Chem. |volume=26 |issue=8 |pages=2085–2091 |date=May 2018 |pmid=29548784 |pmc=5963687 |doi=10.1016/j.bmc.2018.03.007 |url=}}</ref>
|
* One of the most important mediator of angiogenesis
* promotes smooth muscle cells migration and proliferation
|
* Promotes angiogenesis
* Promotes survival
|-
|style="background:#DCDCDC;" align="center" + |Focal adhesion kinase (FAK)<ref name="pmid10436008">{{cite journal |vauthors=Shen Y, Schaller MD |title=Focal adhesion targeting: the critical determinant of FAK regulation and substrate phosphorylation |journal=Mol. Biol. Cell |volume=10 |issue=8 |pages=2507–18 |date=August 1999 |pmid=10436008 |pmc=25482 |doi=10.1091/mbc.10.8.2507 |url=}}</ref><ref name="pmid21118706">{{cite journal |vauthors=Zhao X, Guan JL |title=Focal adhesion kinase and its signaling pathways in cell migration and angiogenesis |journal=Adv. Drug Deliv. Rev. |volume=63 |issue=8 |pages=610–5 |date=July 2011 |pmid=21118706 |pmc=3132829 |doi=10.1016/j.addr.2010.11.001 |url=}}</ref><ref name="pmid26622614">{{cite journal |vauthors=Li M, Hong LI, Liao M, Guo G |title=Expression and clinical significance of focal adhesion kinase and adrenomedullin in epithelial ovarian cancer |journal=Oncol Lett |volume=10 |issue=2 |pages=1003–1007 |date=August 2015 |pmid=26622614 |pmc=4508992 |doi=10.3892/ol.2015.3278 |url=}}</ref>
|
* Promotes endothelial cells migration
* May play a role in integrin-dependent cell survival signal
* Inhibits apoptosis
* Enhances cell motility
|
* Promotes angiogenesis
* Promotes tumor cells survival
* Inhibits apoptosis
* Promotes tumor metastasis
|-
|style="background:#DCDCDC;" align="center" + |E-cadherin<ref name="pmid22543706">{{cite journal |vauthors=Dong LL, Liu L, Ma CH, Li JS, Du C, Xu S, Han LH, Li L, Wang XW |title=E-cadherin promotes proliferation of human ovarian cancer cells in vitro via activating MEK/ERK pathway |journal=Acta Pharmacol. Sin. |volume=33 |issue=6 |pages=817–22 |date=June 2012 |pmid=22543706 |pmc=4010376 |doi=10.1038/aps.2012.30 |url=}}</ref><ref name="pmid14613514">{{cite journal |vauthors=Pećina-Slaus N |title=Tumor suppressor gene E-cadherin and its role in normal and malignant cells |journal=Cancer Cell Int. |volume=3 |issue=1 |pages=17 |date=October 2003 |pmid=14613514 |pmc=270068 |doi=10.1186/1475-2867-3-17 |url=}}</ref><ref name="pmid27582386">{{cite journal |vauthors=Petrova YI, Schecterson L, Gumbiner BM |title=Roles for E-cadherin cell surface regulation in cancer |journal=Mol. Biol. Cell |volume=27 |issue=21 |pages=3233–3244 |date=November 2016 |pmid=27582386 |pmc=5170857 |doi=10.1091/mbc.E16-01-0058 |url=}}</ref>
|
* One of the most important promoter of cell-cell adhesion
* Play critical role in formation and maintenance of epithelia, and tissue formation
|
* Loss or mutations results in
** epithelial–mesenchymal transition
** decreased cell-cell adhesion
** tumor cells invasion
** metastasis
|}
==References==
{{reflist|2}}

Revision as of 16:45, 28 February 2019