HEPACAM
{{Short description|Protein-coding gene in the species Homo sapiens}}
display{{infobox_gene}}
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.{{cite journal | vauthors = Chung Moh M, Hoon Lee L, Shen S | title = Cloning and characterization of hepaCAM, a novel Ig-like cell adhesion molecule suppressed in human hepatocellular carcinoma | journal = Journal of Hepatology | volume = 42 | issue = 6 | pages = 833–841 | date = June 2005 | pmid = 15885354 | doi = 10.1016/j.jhep.2005.01.025 }} 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.
(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.{{cite journal | vauthors = Moh MC, Lee LH, Yang X, Shen S | title = HEPN1, a novel gene that is frequently down-regulated in hepatocellular carcinoma, suppresses cell growth and induces apoptosis in HepG2 cells | journal = Journal of Hepatology | volume = 39 | issue = 4 | pages = 580–586 | date = October 2003 | pmid = 12971969 | doi = 10.1016/S0168-8278(03)00359-3 }} Based on the sequence of HEPN1, the new gene HEPACAM was then isolated and characterised.{{cite journal | vauthors = Moh MC, Zhang C, Luo C, Lee LH, Shen S | title = Structural and functional analyses of a novel ig-like cell adhesion molecule, hepaCAM, in the human breast carcinoma MCF7 cells | journal = The Journal of Biological Chemistry | volume = 280 | issue = 29 | pages = 27366–27374 | date = July 2005 | pmid = 15917256 | doi = 10.1074/jbc.M500852200 | doi-access = free }}
Characteristics and functions
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.{{cite journal | vauthors = Moh MC, Zhang T, Lee LH, Shen S | title = Expression of hepaCAM is downregulated in cancers and induces senescence-like growth arrest via a p53/p21-dependent pathway in human breast cancer cells | journal = Carcinogenesis | volume = 29 | issue = 12 | pages = 2298–2305 | date = December 2008 | pmid = 18845560 | doi = 10.1093/carcin/bgn226 | doi-access = free }} Functionally, hepaCAM is involved in cell-extracellular matrix interactions and growth control of cancer cells, and is able to induce differentiation of glioblastoma cells.{{cite journal | vauthors = Lee LH, Moh MC, Zhang T, Shen S | title = The immunoglobulin-like cell adhesion molecule hepaCAM induces differentiation of human glioblastoma U373-MG cells | journal = Journal of Cellular Biochemistry | volume = 107 | issue = 6 | pages = 1129–1138 | date = August 2009 | pmid = 19507233 | doi = 10.1002/jcb.22215 | s2cid = 21271941 | doi-access = free }} In cell signaling, hepaCAM directly interacts with F-actin{{cite journal | vauthors = Moh MC, Tian Q, Zhang T, Lee LH, Shen S | title = The immunoglobulin-like cell adhesion molecule hepaCAM modulates cell adhesion and motility through direct interaction with the actin cytoskeleton | journal = Journal of Cellular Physiology | volume = 219 | issue = 2 | pages = 382–391 | date = May 2009 | pmid = 19142852 | doi = 10.1002/jcp.21685 | s2cid = 206047365 }} and calveolin 1,{{cite journal | vauthors = Moh MC, Lee LH, Zhang T, Shen S | title = Interaction of the immunoglobulin-like cell adhesion molecule hepaCAM with caveolin-1 | journal = Biochemical and Biophysical Research Communications | volume = 378 | issue = 4 | pages = 755–760 | date = January 2009 | pmid = 19059381 | doi = 10.1016/j.bbrc.2008.11.119 }} and is capable of inducing senescence-like growth arrest via a p53/p21-dependent pathway. Moreover, hepaCAM is proteolytically cleaved near the transmembrane region.{{cite journal | vauthors = Zhang T, Moh MC, Lee LH, Shen S | title = The immunoglobulin-like cell adhesion molecule hepaCAM is cleaved in the human breast carcinoma MCF7 cells | journal = International Journal of Oncology | volume = 37 | issue = 1 | pages = 155–165 | date = July 2010 | pmid = 20514407 | doi = 10.3892/ijo_00000663 | doi-access = free }} These findings indicate that the new Ig-like cell adhesion molecule hepaCAM is also a tumour suppressor.{{cite journal | vauthors = Moh MC, Shen S | title = The roles of cell adhesion molecules in tumor suppression and cell migration: a new paradox | journal = Cell Adhesion & Migration | volume = 3 | issue = 4 | pages = 334–336 | year = 2009 | pmid = 19949308 | pmc = 2802741 | doi = 10.4161/cam.3.4.9246 }}
Mutations in the human HEPACAM gene are linked to forms of leukodystrophy, a group of inherited disorders characterized by degeneration of brain white matter.{{cite journal | vauthors = López-Hernández T, Ridder MC, Montolio M, Capdevila-Nortes X, Polder E, Sirisi S, Duarri A, Schulte U, Fakler B, Nunes V, Scheper GC, Martínez A, Estévez R, van der Knaap MS | display-authors = 6 | title = Mutant GlialCAM causes megalencephalic leukoencephalopathy with subcortical cysts, benign familial macrocephaly, and macrocephaly with retardation and autism | journal = American Journal of Human Genetics | volume = 88 | issue = 4 | pages = 422–432 | date = April 2011 | pmid = 21419380 | pmc = 3071909 | doi = 10.1016/j.ajhg.2011.02.009 }} 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.{{cite journal | vauthors = Jeworutzki E, López-Hernández T, Capdevila-Nortes X, Sirisi S, Bengtsson L, Montolio M, Zifarelli G, Arnedo T, Müller CS, Schulte U, Nunes V, Martínez A, Jentsch TJ, Gasull X, Pusch M, Estévez R | display-authors = 6 | title = GlialCAM, a protein defective in a leukodystrophy, serves as a ClC-2 Cl(-) channel auxiliary subunit | journal = Neuron | volume = 73 | issue = 5 | pages = 951–961 | date = March 2012 | pmid = 22405205 | pmc = 3334819 | doi = 10.1016/j.neuron.2011.12.039 }}{{cite journal | vauthors = Blanz J, Schweizer M, Auberson M, Maier H, Muenscher A, Hübner CA, Jentsch TJ | title = Leukoencephalopathy upon disruption of the chloride channel ClC-2 | journal = The Journal of Neuroscience | volume = 27 | issue = 24 | pages = 6581–6589 | date = June 2007 | pmid = 17567819 | pmc = 6672451 | doi = 10.1523/JNEUROSCI.0338-07.2007 }}
Other names
- glialCAM, which was cloned from a human brain cDNA library in 2008 and found to be identical to hepaCAM;{{cite journal | vauthors = Favre-Kontula L, Rolland A, Bernasconi L, Karmirantzou M, Power C, Antonsson B, Boschert U | title = GlialCAM, an immunoglobulin-like cell adhesion molecule is expressed in glial cells of the central nervous system | journal = Glia | volume = 56 | issue = 6 | pages = 633–645 | date = April 2008 | pmid = 18293412 | doi = 10.1002/glia.20640 | s2cid = 27263006 }} and
- HEPACAM1, when HEPACAM2 emerged in 2010.{{cite journal | vauthors = Klopfleisch R, Klose P, da Costa A, Brunnberg L, Gruber AD | title = HEPACAM1 and 2 are differentially regulated in canine mammary adenomas and carcinomas and its lymph node metastases | journal = BMC Veterinary Research | volume = 6 | pages = 15 | date = March 2010 | pmid = 20226097 | pmc = 2842258 | doi = 10.1186/1746-6148-6-15 | doi-access = free }}
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.