CKLF like MARVEL transmembrane domain-containing 8 explained

CKLF like MARVEL transmembrane domain-containing 8 (i.e. CMTM8), previously termed chemokine-like factor superfamily 8 (i.e. CKLFSF8) has at least two isoforms, the CMTM8 and CMTM8-v2 proteins.^[1] Protein isoforms are variant products that are made by the alternative splicing of a single gene. The gene for these isoforms, CMTM8 (formerly termed CKLFSF8), is located in band 22 on the short (i.e. "p") arm of chromosome 3.^[2] The CMTM8 gene and its CMTM8 and CMTM8-v2 proteins belong to the CKLF-like MARVEL transmembrane domain-containing family of structurally and functionally related genes and proteins.^[3] The CMTM8 protein is the full-length and predominant product of the CMTM8 gene. This protein is expressed in a wide range of normal adult and fetal tissues while relatively little is known about the CMTM8-v2 protein.^[4] Studies suggest that the CMTM8 protein may be involved in the development of various cancers.^[5]

The levels of CMTM8 protein are lower in the tissues of non-small-cell lung carcinoma, colon cancer, rectal cancer, esophageal cancer,^[1] bladder cancer,^[6] stomach cancer,^[7] and glioblastoma brain tumors than in their respective adjacent normal organ tissues. The low levels of CMTM8 protein in bladder and stomach cancer tissues were associated with more aggressive diseases (e.g. presence of metastases) and poorer prognoses. These findings suggest that CMTM8 protein may inhibit the development and/or progression of the cited malignancies and therefore the CMTM8 gene functions as a tumor suppressor gene. However, further studies are required to support these conclusions and to determine if the levels of CMTM8 protein can be used as prognostic markers for these malignancies and/or as a targets for treating them.

Notes and References

1. Zhang W, Qi H, Mo X, Sun Q, Li T, Song Q, Xu K, Hu H, Ma D, Wang Y . CMTM8 is Frequently Downregulated in Multiple Solid Tumors . Applied Immunohistochemistry & Molecular Morphology . 25 . 2 . 122–128 . February 2017 . 26574634 . 10.1097/PAI.0000000000000274 . 205912507 .
2. Duan HJ, Li XY, Liu C, Deng XL . Chemokine-like factor-like MARVEL transmembrane domain-containing family in autoimmune diseases . Chinese Medical Journal . 133 . 8 . 951–958 . April 2020 . 32195671 . 7176445 . 10.1097/CM9.0000000000000747 .
3. Han W, Ding P, Xu M, Wang L, Rui M, Shi S, Liu Y, Zheng Y, Chen Y, Yang T, Ma D . Identification of eight genes encoding chemokine-like factor superfamily members 1-8 (CKLFSF1-8) by in silico cloning and experimental validation . Genomics . 81 . 6 . 609–17 . June 2003 . 12782130 . 10.1016/s0888-7543(03)00095-8 .
4. Li M, Luo F, Tian X, Yin S, Zhou L, Zheng S . Chemokine-Like Factor-Like MARVEL Transmembrane Domain-Containing Family in Hepatocellular Carcinoma: Latest Advances . Frontiers in Oncology . 10 . 595973 . 2020 . 33282744 . 7691587 . 10.3389/fonc.2020.595973 . free .
5. Wu J, Li L, Wu S, Xu B . CMTM family proteins 1-8: roles in cancer biological processes and potential clinical value . Cancer Biology & Medicine . 17 . 3 . 528–542 . August 2020 . 32944388 . 7476098 . 10.20892/j.issn.2095-3941.2020.0032 .
6. Gao D, Hu H, Wang Y, Yu W, Zhou J, Wang X, Wang W, Zhou C, Xu K . CMTM8 inhibits the carcinogenesis and progression of bladder cancer . Oncology Reports . 34 . 6 . 2853–63 . December 2015 . 26503336 . 4722886 . 10.3892/or.2015.4310 .
7. Yan M, Zhu X, Qiao H, Zhang H, Xie W, Cai J . Downregulated CMTM8 Correlates with Poor Prognosis in Gastric Cancer Patients . DNA and Cell Biology . 40 . 6 . 791–797 . June 2021 . 33978454 . 10.1089/dna.2021.0110 . 234473652 .