CKLF-like MARVEL transmembrane domain-containing protein 3 (i.e. CMTM3), also termed chemokine-like factor superfamily 3 (i.e. CKLFSF3), is a member of the
CKLF-like MARVEL transmembrane domain-containing family The CKLF-like MARVEL transmembrane domain-containing family (CMTM), previously termed the chemokine-like factor superfamily (CKLFSF), consists of 9 proteins, some of which have various isoforms due to alternative splicing of their respective genes. ...
(i.e. CMTM) of proteins. In humans, CMTM2 protein is encoded by the ''CMTM3''
gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
located in
band
Band or BAND may refer to:
Places
*Bánd, a village in Hungary
* Band, Iran, a village in Urmia County, West Azerbaijan Province, Iran
* Band, Mureș, a commune in Romania
* Band-e Majid Khan, a village in Bukan County, West Azerbaijan Province, ...
chromosome 16
Chromosome 16 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 16 spans about 90 million base pairs (the building material of DNA) and represents just under 3% of the total DNA in ce ...
. This protein is expressed in a wide range of tissues, including fetal tissues. It is highly expressed in the
male reproductive system
The male reproductive system consists of a number of sex organs that play a role in the process of human reproduction. These organs are located on the outside of the body and within the pelvis.
The main male sex organs are the penis and the t ...
, particularly testicular tissues and may play a role in the development of this tissue. It is also highly expressed in the
immune system
The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as Tumor immunology, cancer cells and objects such ...
including circulating blood cells, i.e.
B lymphocytes
B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or ...
,
CD4+ T lymphocytes
The T helper cells (Th cells), also known as CD4+ cells or CD4-positive cells, are a type of T cell that play an important role in the adaptive immune system. They aid the activity of other immune cells by releasing cytokines. They are consider ...
, and
monocytes
Monocytes are a type of leukocyte or white blood cell. They are the largest type of leukocyte in blood and can differentiate into macrophages and conventional dendritic cells. As a part of the vertebrate innate immune system monocytes also infl ...
. However, CMTM3 protein is weakly expressed or unexpressed in the malignant tissues of several types of cancers. In many but not all of theses cancers, this decreased or lack of expression appears due to
methylation
In the chemical sciences, methylation denotes the addition of a methyl group on a substrate, or the substitution of an atom (or group) by a methyl group. Methylation is a form of alkylation, with a methyl group replacing a hydrogen atom. These t ...
promoter region
In genetics, a promoter is a sequence of DNA to which proteins bind to initiate transcription of a single RNA transcript from the DNA downstream of the promoter. The RNA transcript may encode a protein (mRNA), or can have a function in and of ...
, and thereby the
silencing
Silencing is a visual illusion in which a set of objects that change iluminancehue
Studies of CMTM3 protein levels in normal ''versus'' malignant tissues found that the malignant tissue levels of several types of cancer were lower, in a variable percentage of cases, than the levels in the normal tissues as well as the cases with high CMTM2 levels in the same cancer type. These cancers included those of the stomach, breast,
nasopharynx
The pharynx (plural: pharynges) is the part of the throat behind the mouth and nasal cavity, and above the oesophagus and trachea (the tubes going down to the stomach and the lungs). It is found in vertebrates and invertebrates, though its struc ...
(e.g.
oral squamous cell carcinoma
Squamous-cell carcinomas (SCCs), also known as epidermoid carcinomas, comprise a number of different types of cancer that begin in squamous cells. These cells form on the surface of the skin, on the lining of hollow organs in the body, and on the ...
esophagus
The esophagus (American English) or oesophagus (British English; both ), non-technically known also as the food pipe or gullet, is an organ in vertebrates through which food passes, aided by peristaltic contractions, from the pharynx to the ...
,
prostate gland
The prostate is both an accessory gland of the male reproductive system and a muscle-driven mechanical switch between urination and ejaculation. It is found only in some mammals. It differs between species anatomically, chemically, and physi ...
, colon, and kidney (i.e. the kidney clear-cell type). Moreover, low cancer tissue levels of CTMT3 protein were found to be associated with poorer prognoses compared to cases with higher levels of this protein in cancers of the stomach, esophagus, nasopharynx (i.e. oral squamous cell carcinoma type), and prostate gland. These finding suggest that the CMTM3 protein may act to suppress the development and/or progression of these cancers. Further studies are needed to support this suggestion and determine if CMTM3 protein can be a useful clinical marker to predict the severity of these cancers and/or serve as a therapeutic target for treating them.
Contrastingly, other studies have reported that: 1) CMTM3 protein promoted the proliferation of cultured glioblastoma immortalized cells; 2) high levels of CMTM3 protein were associated with shorter survival times in individuals with glioblastomas and gastric cancer; 3) analyses of 178 patients with pancreatic cancer found that their tumor tissues had higher CMTM3 protein levels than normal nearby pancreas tissues; and 4) patients with high levels of CMTM3 protein in their pancreatic cancer tissues had poorer prognoses and overall survival rates compared to patients with lower CMTM3 levels in their pancreatic cancer tissues. These findings suggest that CMTM3 acts to promote the development and/or progression of these three cancer types. They support further studies to confirm this suggestion, to determine if CMTM3 can be use as a prognostic indicator and a clinical therapeutic target for these three cancer types. Further investigations into the mechanisms behind the apparent ability of CMTM3 to suppress or promote these cancers are also needed.