display 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. The gene encodes a protein of 416 amino acids, designated as hepaCAM**, which is a new member of the

immunoglobulin superfamily The immunoglobulin superfamily (IgSF) is a large protein superfamily of cell surface and soluble proteins that are involved in the recognition, binding, or adhesion processes of cells. Molecules are categorized as members of this superfamily ...

cell adhesion molecule Cell adhesion molecules (CAMs) are a subset of cell surface proteins that are involved in the binding of cells with other cells or with the extracellular matrix (ECM), in a process called cell adhesion. In essence, CAMs help cells stick to each ...

s (

IgSF CAM IgSF CAMs (Immunoglobulin-like Cell Adhesion Molecules) are cell adhesion molecules that belong to Immunoglobulin superfamily. It is regarded as the most diverse superfamily of CAMs. This family is characterized by their extracellular domains cont ...

). The main biological functions of hepaCAM include a) modulating cell-matrix adhesion and

migration Migration, migratory, or migrate may refer to: Human migration * Human migration, physical movement by humans from one region to another ** International migration, when peoples cross state boundaries and stay in the host state for some minimum le ...

, and b) inhibiting

cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...

cell growth Cell most often refers to: * Cell (biology), the functional basic unit of life * Cellphone, a phone connected to a cellular network * Clandestine cell, a penetration-resistant form of a secret or outlawed organization * Electrochemical cell, a de ...

. (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 Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults and is currently the most common cause of death in people with cirrhosis. HCC is the third leading cause of cancer-related deaths worldwide. HCC most common ...

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 Glycoproteins are proteins which contain oligosaccharide (sugar) chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known a ...

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. Functionally, hepaCAM is involved in cell-extracellular matrix interactions and growth control of cancer cells, and is able to induce differentiation of

glioblastoma Glioblastoma, previously known as glioblastoma multiforme (GBM), is the most aggressive and most common type of cancer that originates in the brain, and has a very poor prognosis for survival. Initial signs and symptoms of glioblastoma are nons ...

cells. In cell signaling, hepaCAM directly interacts with

F-actin Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of ...

and calveolin 1, and is capable of inducing senescence-like growth arrest via a p53/p21-dependent pathway. Moreover, hepaCAM is proteolytically cleaved near the transmembrane region. 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 Leukodystrophies are a group of, usually, inherited disorders, characterized by degeneration of the white matter in the brain. The word ''leukodystrophy'' comes from the Greek roots ''leuko'', "white", ''dys'', "abnormal" and ''troph'', "growth". ...

, 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 Membrane protein MLC1 is a protein that in humans is encoded by the ''MLC1'' gene. MLC1 (also called ''WKL1'') is the only human gene currently associated with megalencephalic leukoencephalopathy with subcortical cysts (MLC). Evidence exists fo ...

and CLCN2, two other human genes linked to leukodystrophies.

Other names

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

About HEPACAM 2

Metastatic Metastasis is a pathogenic agent's spreading from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, ...

canine Canine may refer to: Zoology and anatomy * Animals of the family Canidae, more specifically the subfamily Caninae, which includes dogs, wolves, foxes, jackals and coyotes ** ''Canis'', a genus that includes dogs, wolves, coyotes, and jackals ** Do ...

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

References

{{DEFAULTSORT:Hepacam Breast cancer Immunoglobulin superfamily Tumor suppressor genes