Biology:HEPACAM
 Generic protein structure example |
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.[1] 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 cancer cell growth.[1]
(Note: *HEPACAM, gene name; **hepaCAM, protein name)
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 proteolytically cleaved near the transmembrane region.[8] These findings indicate that the new Ig-like cell adhesion molecule hepaCAM is also a tumour suppressor.[9]
Mutations in the human HEPACAM gene are linked to forms of leukodystrophy, a group of inherited disorders characterized by degeneration of brain white matter.[10] The protein produced from the HEPACAM gene was found to interact with the gene products of MLC1 and CLCN2, two other human genes linked to leukodystrophies.[10][11][12]
Other names
- glialCAM, which was cloned from a human brain cDNA library in 2008 and found to be identical to hepaCAM;[13] and
- HEPACAM1, when HEPACAM2 emerged in 2010.[14]
About HEPACAM 2
Metastatic canine mammary carcinoma and their metastases are characterized by decreased HEPACAM2 but unchanged HEPACAM2 expression levels when compared to normal glands.[14]
References
- ↑ 1.0 1.1 "Cloning and characterization of hepaCAM, a novel Ig-like cell adhesion molecule suppressed in human hepatocellular carcinoma". Journal of Hepatology 42 (6): 833–841. June 2005. doi:10.1016/j.jhep.2005.01.025. PMID 15885354.
- ↑ "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. October 2003. doi:10.1016/S0168-8278(03)00359-3. PMID 12971969.
- ↑ 3.0 3.1 3.2 "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): 27366–27374. July 2005. doi:10.1074/jbc.M500852200. PMID 15917256.
- ↑ 4.0 4.1 "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): 2298–2305. December 2008. doi:10.1093/carcin/bgn226. PMID 18845560.
- ↑ "The immunoglobulin-like cell adhesion molecule hepaCAM induces differentiation of human glioblastoma U373-MG cells". Journal of Cellular Biochemistry 107 (6): 1129–1138. August 2009. doi:10.1002/jcb.22215. PMID 19507233.
- ↑ "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. May 2009. doi:10.1002/jcp.21685. PMID 19142852.
- ↑ "Interaction of the immunoglobulin-like cell adhesion molecule hepaCAM with caveolin-1". Biochemical and Biophysical Research Communications 378 (4): 755–760. January 2009. doi:10.1016/j.bbrc.2008.11.119. PMID 19059381.
- ↑ "The immunoglobulin-like cell adhesion molecule hepaCAM is cleaved in the human breast carcinoma MCF7 cells". International Journal of Oncology 37 (1): 155–165. July 2010. doi:10.3892/ijo_00000663. PMID 20514407.
- ↑ "The roles of cell adhesion molecules in tumor suppression and cell migration: a new paradox". Cell Adhesion & Migration 3 (4): 334–336. 2009. doi:10.4161/cam.3.4.9246. PMID 19949308.
- ↑ 10.0 10.1 "Mutant GlialCAM causes megalencephalic leukoencephalopathy with subcortical cysts, benign familial macrocephaly, and macrocephaly with retardation and autism". American Journal of Human Genetics 88 (4): 422–432. April 2011. doi:10.1016/j.ajhg.2011.02.009. PMID 21419380.
- ↑ "GlialCAM, a protein defective in a leukodystrophy, serves as a ClC-2 Cl(-) channel auxiliary subunit". Neuron 73 (5): 951–961. March 2012. doi:10.1016/j.neuron.2011.12.039. PMID 22405205.
- ↑ "Leukoencephalopathy upon disruption of the chloride channel ClC-2". The Journal of Neuroscience 27 (24): 6581–6589. June 2007. doi:10.1523/JNEUROSCI.0338-07.2007. PMID 17567819.
- ↑ "GlialCAM, an immunoglobulin-like cell adhesion molecule is expressed in glial cells of the central nervous system". Glia 56 (6): 633–645. April 2008. doi:10.1002/glia.20640. PMID 18293412.
- ↑ 14.0 14.1 "HEPACAM1 and 2 are differentially regulated in canine mammary adenomas and carcinomas and its lymph node metastases". BMC Veterinary Research 6: 15. March 2010. doi:10.1186/1746-6148-6-15. PMID 20226097.
 |  |
