Gene HEPACAM*, 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 in human liver and reported by Shali Shen (MD, PhD) in 2005.[5] The gene encodes a protein of 416 amino acids, designated as hepaCAM**, which is a new member of the immunoglobulin superfamily of cell adhesion molecules (IgSF CAM). The main biological functions of hepaCAM include a) modulating cell-matrix adhesion and migration, and b) inhibiting cancercell growth.[5]
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.[6] Based on the sequence of HEPN1, the new gene HEPACAM was then isolated and characterised.[7]
Structurally, hepaCAM is a glycoprotein 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 of glioblastoma cells.[9] In cell signaling, hepaCAM directly interacts with F-actin[10] and calveolin 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 transmemberane region.[12] These findings indicate that the new Ig-like cell adhesion molecule hepaCAM is also a tumour suppressor.[13]
Metastaticcaninemammary carcinoma and their metastases are characterized by decreased HEPACAM2 but unchanged HEPACAM2 expression levels when compared to normal glands.[15]
^"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): 833–41. 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.
^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): 382–91. 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): 755–60. doi:10.1016/j.bbrc.2008.11.119. PMID19059381.
^Favre-Kontula L, Rolland A, Bernasconi L, et al. (April 2008). "GlialCAM, an immunoglobulin-like cell adhesion molecule is expressed in glial cells of the central nervous system". Glia. 56 (6): 633–45. doi:10.1002/glia.20640. PMID18293412. S2CID27263006.
