HEPACAM

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. Based on the sequence of HEPN1, the new gene HEPACAM was then isolated and characterised.

Characteristics and functions

Structurally, hepaCAM is a glycoprotein containing an extracellular domain with 2 Ig-like loops, a transmembrane region and a cytoplasmic domain. Functionally, hepaCAM is involved in cell-extracellular matrix interactions and growth control of cancer 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. These findings indicate that the new Ig-like cell adhesion molecule hepaCAM is also a tumour suppressor.

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

Other names

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

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.

References

References

1. (June 2005). "Cloning and characterization of hepaCAM, a novel Ig-like cell adhesion molecule suppressed in human hepatocellular carcinoma". Journal of Hepatology.
2. (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.
3. (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.
4. (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.
5. (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.
6. (January 2009). "Interaction of the immunoglobulin-like cell adhesion molecule hepaCAM with caveolin-1". Biochemical and Biophysical Research Communications.
7. (July 2010). "The immunoglobulin-like cell adhesion molecule hepaCAM is cleaved in the human breast carcinoma MCF7 cells". International Journal of Oncology.
8. (2009). "The roles of cell adhesion molecules in tumor suppression and cell migration: a new paradox". Cell Adhesion & Migration.
9. (April 2011). "Mutant GlialCAM causes megalencephalic leukoencephalopathy with subcortical cysts, benign familial macrocephaly, and macrocephaly with retardation and autism". American Journal of Human Genetics.
10. (March 2012). "GlialCAM, a protein defective in a leukodystrophy, serves as a ClC-2 Cl(-) channel auxiliary subunit". Neuron.
11. (June 2007). "Leukoencephalopathy upon disruption of the chloride channel ClC-2". The Journal of Neuroscience.
12. (April 2008). "GlialCAM, an immunoglobulin-like cell adhesion molecule is expressed in glial cells of the central nervous system". Glia.
13. (March 2010). "HEPACAM1 and 2 are differentially regulated in canine mammary adenomas and carcinomas and its lymph node metastases". BMC Veterinary Research.