GeneHEPACAM*, named based on its original site of identification -hepatocytes and the nature of its protein product - a cell adhesion molecule (CAM), was first discovered and characterised inhuman liver.[5] The gene encodes a protein of 416 amino acids, designated as hepaCAM**, which is a new member of theimmunoglobulin superfamily ofcell adhesion molecules (IgSF CAM). The main biological functions of hepaCAM include a) modulating cell-matrix adhesion andmigration, and b) inhibitingcancercell growth.[5]
(Note: *HEPACAM, gene name; **hepaCAM, protein name)
Through differential screening of gene expression, over 200 genes were found to be either up- or down-regulated in ahepatocellular carcinoma patient. These genes were subsequently evaluated against a panel of human HCC specimens, leading to the identification of a novel geneHEPN1.[6] Based on the sequence of HEPN1, the new gene HEPACAM was then isolated and characterised.[7]
Structurally, hepaCAM is aglycoprotein containing an extracellular domain with 2 Ig-like loops, a transmembrane region and a cytoplasmic domain.[7] 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.[8] Functionally, hepaCAM is involved in cell-extracellular matrix interactions and growth control of cancer cells,[7] and is able to induce differentiation ofglioblastoma cells.[9] In cell signaling, hepaCAM directly interacts withF-actin[10] andcalveolin 1,[11] and is capable of inducing senescence-like growth arrest via a p53/p21-dependent pathway.[8] Moreover, hepaCAM is proteolytically cleaved near the transmembrane region.[12] These findings indicate that the new Ig-like cell adhesion molecule hepaCAM is also atumour suppressor.[13]
Mutations in the human HEPACAM gene are linked to forms ofleukodystrophy, a group of inherited disorders characterized by degeneration of brain white matter.[14] The protein produced from the HEPACAM gene was found to interact with the gene products ofMLC1 andCLCN2, two other human genes linked to leukodystrophies.[14][15][16]
Metastaticcaninemammary carcinoma and their metastases are characterized by decreased HEPACAM2 but unchanged HEPACAM2 expression levels when compared to normal glands.[18]
^"Human PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^abChung 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):833–841.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):580–586.doi:10.1016/S0168-8278(03)00359-3.PMID12971969.
^Moh 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):382–391.doi:10.1002/jcp.21685.PMID19142852.S2CID206047365.
^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):755–760.doi:10.1016/j.bbrc.2008.11.119.PMID19059381.
^Favre-Kontula L, Rolland A, Bernasconi L, Karmirantzou M, Power C, Antonsson B, Boschert U (April 2008). "GlialCAM, an immunoglobulin-like cell adhesion molecule is expressed in glial cells of the central nervous system".Glia.56 (6):633–645.doi:10.1002/glia.20640.PMID18293412.S2CID27263006.
