View source for HEPACAM

{{Short description|Protein-coding gene in the species Homo sapiens}}
display{{infobox_gene}}
Gene '''HEPACAM'''*, named based on its original site of identification - '''hepa'''tocytes and the nature of its protein product - a cell adhesion molecule ('''CAM'''), was first discovered and characterised in [[human liver]].<ref name=pmid15885354>{{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 }}</ref> The gene encodes a protein of 416 amino acids, designated as hepaCAM**, which is a new member of the [[IgSF CAM|immunoglobulin superfamily]] of [[cell adhesion molecule]]s ([[IgSF CAM]]). The main biological functions of hepaCAM include a) modulating cell-matrix adhesion and [[Cell migration|migration]], and b) inhibiting [[cancer]] [[cell growth]].<ref name=pmid15885354/>
(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]].<ref>{{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 }}</ref> Based on the sequence of HEPN1, the new gene HEPACAM was then isolated and characterised.<ref name=pmid15917256>{{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 }}</ref>
==Characteristics and functions==
Structurally, hepaCAM is a [[glycoprotein]] containing an extracellular domain with 2 Ig-like loops, a transmembrane region and a cytoplasmic domain.<ref name=pmid15917256/> 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.<ref name=pmid18845560>{{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 }}</ref> Functionally, hepaCAM is involved in cell-extracellular matrix interactions and growth control of cancer cells,<ref name=pmid15917256/> and is able to induce differentiation of [[glioblastoma]] cells.<ref>{{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 }}</ref> In cell signaling, hepaCAM directly interacts with [[F-actin]]<ref name=pmid19142852>{{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 }}</ref> and [[Caveolin 1|calveolin 1]],<ref>{{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 }}</ref> and is capable of inducing senescence-like growth arrest via a p53/p21-dependent pathway.<ref name=pmid18845560/> Moreover, hepaCAM is proteolytically cleaved near the transmembrane region.<ref>{{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 }}</ref> These findings indicate that the new Ig-like cell adhesion molecule hepaCAM is also a [[tumor suppressor gene|tumour suppressor]].<ref>{{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 }}</ref>
Mutations in the human HEPACAM gene are linked to forms of [[leukodystrophy]], a group of inherited disorders characterized by degeneration of brain white matter.<ref name=":0">{{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 }}</ref> 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.<ref name=":0" /><ref>{{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 }}</ref><ref>{{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 }}</ref>
==Other names==
#glialCAM, which was cloned from a human brain cDNA library in 2008 and found to be identical to hepaCAM;<ref name=pmid18293412>{{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 }}</ref> and
#HEPACAM1, when HEPACAM2 emerged in 2010.<ref name=pmid20226097>{{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 }}</ref>
==About HEPACAM 2==
[[Metastatic]] [[domestic dog|canine]] [[mammary carcinoma]] and their metastases are characterized by decreased HEPACAM2 but unchanged HEPACAM2 expression levels when compared to normal glands.<ref name=pmid20226097/>
== References ==
{{Reflist}}
{{DEFAULTSORT:Hepacam}}
[[Category:Breast cancer]]
[[Category:Immunoglobulin superfamily]]
[[Category:Tumor suppressor genes]]