AEG-1 induces an oncogene called Late SV40 factor (LSF/TFCP2) which is involved in thymidylate synthase (TS) induction and DNA biosynthesis synthesis.[6] Late SV40 factor (LSF/TFCP2) enhances angiogenesis by transcriptionally up-regulating matrix metalloproteinase-9 (MMP9).[7]
Clinical significance
AEG-1 acts as an oncogene in melanoma, malignant glioma, breast cancer and hepatocellular carcinoma.[8] It is highly expressed in these cancers and helps in progression and development of these cancers. It is induced by c-Myc oncogene and plays very important role in anchorage independent growth of cancer cells.
Elevated expression of the metastasis gene metadherin (MTDH), which is overexpressed in more than 40% of breast cancers, is associated with poor clinical outcomes. MTDH has a dual role in promoting metastatic seeding and enhancing chemoresistance. MTDH is therefore a potential therapeutic target for enhancing chemotherapy and reducing metastasis.[9]
LSF/TFCP2 plays multifaceted role in chemo resistance, EMT, allergic response, inflammation and Alzheimer’s disease.[10]
AEG-1 controls many hallmarks of oncogenes and cancer. AEG-1/MTDH induces hepato steatosis in mouse liver.[11] The MTDH knockdown by artificial microRNA interference functions as a potential tumor suppressor in breast cancer.[12] Astrocyte elevated gene-1/MTDH undergoes palmitoylation in normal and abnormal physiology of the cell.[13]The microgrooved biomaterial titanium substrata can alter the expression of AEG-1 in human primary cells.[14]
↑Brown DM, Ruoslahti E (Apr 2004). "Metadherin, a cell surface protein in breast tumors that mediates lung metastasis". Cancer Cell. 5 (4): 365–74. doi:10.1016/S1535-6108(04)00079-0. PMID15093543.
↑Sutherland HG, Lam YW, Briers S, Lamond AI, Bickmore WA (Mar 2004). "3D3/lyric: a novel transmembrane protein of the endoplasmic reticulum and nuclear envelope, which is also present in the nucleolus". Experimental Cell Research. 294 (1): 94–105. doi:10.1016/j.yexcr.2003.11.020. PMID14980505.
↑Lee MH, Kang JH, Lee SW (Apr 2012). "The significance of differential expression of genes and proteins in human primary cells caused by microgrooved biomaterial substrata". Biomaterials. 33 (11): 3216–34. doi:10.1016/j.biomaterials.2012.01.034. PMID22285466.
van 't Veer LJ, Dai H, van de Vijver MJ, He YD, Hart AA, Mao M, Peterse HL, van der Kooy K, Marton MJ, Witteveen AT, Schreiber GJ, Kerkhoven RM, Roberts C, Linsley PS, Bernards R, Friend SH (Jan 2002). "Gene expression profiling predicts clinical outcome of breast cancer". Nature. 415 (6871): 530–6. doi:10.1038/415530a. PMID11823860.
Sutherland HG, Lam YW, Briers S, Lamond AI, Bickmore WA (Mar 2004). "3D3/lyric: a novel transmembrane protein of the endoplasmic reticulum and nuclear envelope, which is also present in the nucleolus". Experimental Cell Research. 294 (1): 94–105. doi:10.1016/j.yexcr.2003.11.020. PMID14980505.
Brown DM, Ruoslahti E (Apr 2004). "Metadherin, a cell surface protein in breast tumors that mediates lung metastasis". Cancer Cell. 5 (4): 365–74. doi:10.1016/S1535-6108(04)00079-0. PMID15093543.
Britt DE, Yang DF, Yang DQ, Flanagan D, Callanan H, Lim YP, Lin SH, Hixson DC (Oct 2004). "Identification of a novel protein, LYRIC, localized to tight junctions of polarized epithelial cells". Experimental Cell Research. 300 (1): 134–48. doi:10.1016/j.yexcr.2004.06.026. PMID15383321.
Kang DC, Su ZZ, Sarkar D, Emdad L, Volsky DJ, Fisher PB (Jun 2005). "Cloning and characterization of HIV-1-inducible astrocyte elevated gene-1, AEG-1". Gene. 353 (1): 8–15. doi:10.1016/j.gene.2005.04.006. PMID15927426.
Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M (Nov 2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–48. doi:10.1016/j.cell.2006.09.026. PMID17081983.