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HEPACAM

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HEPACAM
Identifiers
AliasesHEPACAM, GlialCAM, MLC2A, MLC2B, hepatic and glial cell adhesion molecule, HEPACAM1, HEPN1
External IDsOMIM: 611642; MGI: 1920177; HomoloGene: 17652; GeneCards: HEPACAM; OMA:HEPACAM - orthologs
Orthologs
SpeciesHumanMouse
Entrez

220296

72927

Ensembl

ENSG00000165478

ENSMUSG00000046240

UniProt

Q14CZ8

Q640R3

RefSeq (mRNA)

NM_152722

NM_175189

RefSeq (protein)

NP_689935

NP_780398

Location (UCSC)Chr 11: 124.92 – 124.94 MbChr 9: 37.28 – 37.3 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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.[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 cancer cell growth.[5]

(Note: *HEPACAM, gene name; **hepaCAM, protein name)

Discovery

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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]

Characteristics and functions

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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 transmembrane region.[12] These findings indicate that the new Ig-like cell adhesion molecule hepaCAM is also a tumour suppressor.[13]

Mutations in the human HEPACAM gene are linked to forms of leukodystrophy, a group of inherited disorders characterized by degeneration of brain white matter.[14] 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.[14][15][16]

Other names

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  1. glialCAM, which was cloned from a human brain cDNA library in 2008 and found to be identical to hepaCAM;[17] and
  2. HEPACAM1, when HEPACAM2 emerged in 2010.[18]

About HEPACAM 2

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Metastatic canine mammary carcinoma and their metastases are characterized by decreased HEPACAM2 but unchanged HEPACAM2 expression levels when compared to normal glands.[18]

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000165478 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000046240 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b 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): 833–841. doi:10.1016/j.jhep.2005.01.025. PMID 15885354.
  6. ^ 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): 580–586. doi:10.1016/S0168-8278(03)00359-3. PMID 12971969.
  7. ^ a b c 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): 27366–27374. doi:10.1074/jbc.M500852200. PMID 15917256.
  8. ^ a b 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): 2298–2305. doi:10.1093/carcin/bgn226. PMID 18845560.
  9. ^ 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): 1129–1138. doi:10.1002/jcb.22215. PMID 19507233. S2CID 21271941.
  10. ^ 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): 382–391. doi:10.1002/jcp.21685. PMID 19142852. S2CID 206047365.
  11. ^ 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): 755–760. doi:10.1016/j.bbrc.2008.11.119. PMID 19059381.
  12. ^ 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): 155–165. doi:10.3892/ijo_00000663. PMID 20514407.
  13. ^ 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): 334–336. doi:10.4161/cam.3.4.9246. PMC 2802741. PMID 19949308.
  14. ^ a b López-Hernández T, Ridder MC, Montolio M, Capdevila-Nortes X, Polder E, Sirisi S, et al. (April 2011). "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. doi:10.1016/j.ajhg.2011.02.009. PMC 3071909. PMID 21419380.
  15. ^ Jeworutzki E, López-Hernández T, Capdevila-Nortes X, Sirisi S, Bengtsson L, Montolio M, et al. (March 2012). "GlialCAM, a protein defective in a leukodystrophy, serves as a ClC-2 Cl(-) channel auxiliary subunit". Neuron. 73 (5): 951–961. doi:10.1016/j.neuron.2011.12.039. PMC 3334819. PMID 22405205.
  16. ^ Blanz J, Schweizer M, Auberson M, Maier H, Muenscher A, Hübner CA, Jentsch TJ (June 2007). "Leukoencephalopathy upon disruption of the chloride channel ClC-2". The Journal of Neuroscience. 27 (24): 6581–6589. doi:10.1523/JNEUROSCI.0338-07.2007. PMC 6672451. PMID 17567819.
  17. ^ Favre-Kontula L, Rolland A, Bernasconi L, Karmirantzou M, Power C, Antonsson B, Boschert U (April 2008). "GlialCAM, an immunoglobulin-like cell adhesion molecule is expressed in glial cells of the central nervous system". Glia. 56 (6): 633–645. doi:10.1002/glia.20640. PMID 18293412. S2CID 27263006.
  18. ^ a b Klopfleisch R, Klose P, da Costa A, Brunnberg L, Gruber AD (March 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 2842258. PMID 20226097.