HEPACAM

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]

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]

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]

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