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. 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 adhesion and migration, and b) inhibiting cancer cell growth.
Identification of hepaCAM
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. Based on the sequence of HepN1, the new gene hepaCAM was then isolated and characterised.
Characteristics and functions of hepaCAM
Structurally, hepaCAM is a glycoprotein containing an extracellular domain with 2 Ig-like loops, a transmembrane region and a cytoplasmic domain. 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. Functionally, hepaCAM is involved in cell-extracellular matrix interactions and growth control of cancer cells, and is able to induce differentiation of glioblastoma cells. In cell signaling, hepaCAM directly interacts with F-actin and calveolin 1, and is capable of inducing senescence-like growth arrest via a p53/p21-dependent pathway. Moreover, hepaCAM is proteolystically cleaved near the transmemberane region. These findings indicate that the new Ig-like cell adhesion molecule hepaCAM is also a tumour suppressor.
Other names of hepaCAM
- glialCAM (when hepaCAM was investigated in the CNS in 2008); and
- hepaCAM1 (when hepaCAM2 emerged in 2010).
About hepaCAM 2
The hepatocyte cell adhesion molecules 1 and 2 (HEPACAM 1 and 2) are members of the immunoglobulin family of adhesion genes. HEPACAM1 is involved in negative cell cycle regulation via p53, p21 and p27 signalling but also mediates increased human breast cancer cell spread. Metastatic canine mammary carcinoma and their metastases are characterized by decreased HEPACAM2 but unchanged HEPACAM2 expression levels when compared to normal glands.
- Chung 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. PMID 15885354.
- 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. PMID 12971969.
- Moh 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. PMID 15917256.
- Moh 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. PMID 18845560.
- 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. PMID 19507233.
- 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. PMID 19142852.
- 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. PMID 19059381.
- Zhang T, Moh MC, Lee LH, Shen S (July 2010). "The immunoglobulin-like cell adhesion molecule hepaCAM is cleaved in the human breast carcinoma MCF7 cells". International Journal of Oncology. 37 (1): 155–65. doi:10.3892/ijo_00000663. PMID 20514407.
- Moh MC, Shen S (2009). "The roles of cell adhesion molecules in tumor suppression and cell migration: a new paradox". Cell Adhesion & Migration. 3 (4): 334–6. doi:10.4161/cam.3.4.9246. PMC . PMID 19949308.
- 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. PMID 18293412.
- Klopfleisch R, Klose P, da Costa A, Brunnberg L, Gruber AD (2010). "HEPACAM1 and 2 are differentially regulated in canine mammary adenomas and carcinomas and its lymph node metastases". BMC Veterinary Research. 6: 15. doi:10.1186/1746-6148-6-15. PMC . PMID 20226097.