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 liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it is ...
and reported by Shali Shen (MD, PhD) in 2005.
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 ...
of
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 abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
cell growth
Cell growth refers to an increase in the total mass of a cell, including both cytoplasmic, nuclear and organelle volume. Cell growth occurs when the overall rate of cellular biosynthesis (production of biomolecules or anabolism) is greater than ...
.
[
(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.
It occurs in t ...
patient. These genes were subsequently evaluated against a panel of human HCC specimens, leading to the identification of a novel gene HEPN1
Hepatocellular carcinoma, down-regulated 1 is a protein that in humans is encoded by the HEPN1 gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning '' ...
. 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 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 as glycos ...
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.][ and is able to induce differentiation of ]glioblastoma
Glioblastoma, previously known as glioblastoma multiforme (GBM), is one of the most aggressive types of cancer that begin within the brain. Initially, signs and symptoms of glioblastoma are nonspecific. They may include headaches, personality ch ...
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 ov ...
[ Moreover, hepaCAM is proteolytically cleaved near the transmemberane region. These findings indicate that the new Ig-like cell adhesion molecule hepaCAM is also a tumour suppressor.]
Other names
#glialCAM, which was cloned from a human brain cDNA library in 2008 and found to be identical to hepaCAM;
About HEPACAM 2
Metastatic
Metastasis is a pathogenic agent's spread 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, then, ...
canine mammary carcinoma
Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or a r ...
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