Hepatic and glial cell adhesion molecule (HEPACAM) is a protein encoded by HEPACAM gene. It was first discovered and characterised in human liver cells by Shali Shen in 2005.[1] The protein consists of 416 amino acids, and is a member of the immunoglobulin superfamily of cell adhesion molecules. The main biological functions of HEPACAM include a) modulating cell adhesion and migration, and b) inhibiting cancercell growth.[1]
Discovery
Through differential screening of gene expression, over 200 genes were found to be either up- or down-regulated in a hepatocellular carcinoma patient. These genes were subsequently evaluated against a panel of human HCC specimens, leading to the identification of a novel gene HEPN1.[2] Based on the sequence of HEPN1, the new gene HEPACAM was then isolated and characterised.[3]
Characteristics and functions
Structurally, HEPACAM is a glycoprotein containing an extracellular domain with 2 Ig-like loops, a transmembrane region and a cytoplasmic domain.[3] Matched to chromosome 11q24, gene HEPACAM is ubiquitously expressed in normal human tissues, with particularly high expression levels in the central nervous system (CNS), and is frequently suppressed in a variety of tumour types.[4]
Functionally, HEPACAM is involved in cell-extracellular matrix interactions and growth control of cancer cells,[3] and is able to induce differentiation of glioblastoma cells.[5] In cell signaling, HEPACAM directly interacts with F-actin[6] and calveolin 1,[7] and is capable of inducing senescence-like growth arrest via a p53/p21-dependent pathway.[4] Moreover, HEPACAM is proteolystically cleaved near the transmemberane region.[8] These findings indicate that the new Ig-like cell adhesion molecule HEPACAM is also a tumour suppressor.[9] HEPACAM1 is involved in negative cell cycle regulation via p53, p21 and p27 signalling[4] but also mediates increased human breast cancer cell spread.[3][6]
References
↑ 1.01.1Chung Moh M, Hoon Lee L, Shen S (June 2005). "Cloning and characterization of hepaCAM, a novel Ig-like cell adhesion molecule suppressed in human hepatocellular carcinoma". Journal of Hepatology. 42 (6): 833–41. doi:10.1016/j.jhep.2005.01.025. PMID15885354.
↑Moh MC, Lee LH, Yang X, Shen S (October 2003). "HEPN1, a novel gene that is frequently down-regulated in hepatocellular carcinoma, suppresses cell growth and induces apoptosis in HepG2 cells". Journal of Hepatology. 39 (4): 580–6. doi:10.1016/S0168-8278(03)00359-3. PMID12971969.
↑ 3.03.13.23.3Moh MC, Zhang C, Luo C, Lee LH, Shen S (July 2005). "Structural and functional analyses of a novel ig-like cell adhesion molecule, hepaCAM, in the human breast carcinoma MCF7 cells". The Journal of Biological Chemistry. 280 (29): 27366–74. doi:10.1074/jbc.M500852200. PMID15917256.
↑ 4.04.14.2Moh MC, Zhang T, Lee LH, Shen S (December 2008). "Expression of hepaCAM is downregulated in cancers and induces senescence-like growth arrest via a p53/p21-dependent pathway in human breast cancer cells". Carcinogenesis. 29 (12): 2298–305. doi:10.1093/carcin/bgn226. PMID18845560.
↑Lee LH, Moh MC, Zhang T, Shen S (August 2009). "The immunoglobulin-like cell adhesion molecule hepaCAM induces differentiation of human glioblastoma U373-MG cells". Journal of Cellular Biochemistry. 107 (6): 1129–38. doi:10.1002/jcb.22215. PMID19507233.
↑ 6.06.1Moh MC, Tian Q, Zhang T, Lee LH, Shen S (May 2009). "The immunoglobulin-like cell adhesion molecule hepaCAM modulates cell adhesion and motility through direct interaction with the actin cytoskeleton". Journal of Cellular Physiology. 219 (2): 382–91. doi:10.1002/jcp.21685. PMID19142852.
↑Moh MC, Lee LH, Zhang T, Shen S (January 2009). "Interaction of the immunoglobulin-like cell adhesion molecule hepaCAM with caveolin-1". Biochemical and Biophysical Research Communications. 378 (4): 755–60. doi:10.1016/j.bbrc.2008.11.119. PMID19059381.