Current Opinions on the Relationship Between CMTM Family and Hepatocellular Carcinoma

Figures & data

Figure 1 CMTM family and human tumors. CMTM family is a new protein family with the structure of chemokine and transmembrane 4 superfamily.⁷ And it is closely related with various tumors by regulating cancer cell proliferation, apoptosis and migration.^8–12 The figure is created by authors through using software Adobe Illustrator 2023.

Abbreviation: CMTM, Chemokine-like factor superfamily.

Figure 2 How CMTM4/6 perform in Hepatocellular carcinoma. CMTM4/CMTM6, and PD-L1 interact to make PD-L1 ubiquitinated and non-degradable, upregulating T-cell signaling and promoting antigen presentation, further activating macrophages and reducing T-cell function.¹¹ Furthermore, CMTM6 interacts with P21 to block P21 ubiquitination, block the G1/S phase transition, and inhibit tumor cell proliferation;⁷⁵ Knockdown of CMTM6 results in decreased B7 ligand expression and inhibits tumor cell proliferation;⁷⁶ However, when CMTM6 interacts with Vimentin, inducing EMT and promoting the proliferation of HCC cells.⁷⁷

Abbreviations: CMTM, Chemokine-like factor superfamily; PD-L1, programmed cell death-ligand 1; Mø, macrophages; P21, aioncogene p21 protein; EMT, epithelial-mesenchymal transformation; HCC, Hepatocellular carcinoma.

Han W, Ding P, Xu M, et al. Identification of eight genes encoding chemokine-like factor superfamily members 1–8 (CKLFSF1–8) by in silico cloning and experimental validation. Genomics. 2003;81(6):609–617. doi:10.1016/S0888-7543(03)00095-8

 PubMed Web of Science ®Google Scholar

Mezzadra R, Sun C, Jae LT, et al. Identification of CMTM6 and CMTM4 as PD-L1 protein regulators. Nature. 2017;549(7670):106–110. doi:10.1038/nature23669

 PubMed Web of Science ®Google Scholar

Li H, Liu YT, Chen L, et al. CMTM4 regulates epithelial-mesenchymal transition and PD-L1 expression in head and neck squamous cell carcinoma. Mol Carcinog. 2021;60(8):556–566. doi:10.1002/mc.23323

 PubMed Web of Science ®Google Scholar

Wang Z, Peng Z, Liu Q, et al. Co-expression with membrane CMTM6/4 on tumor epithelium enhances the prediction value of PD-L1 on anti-PD-1/L1 therapeutic efficacy in gastric adenocarcinoma. Cancers. 2021;13(20):5175. doi:10.3390/cancers13205175

 PubMed Web of Science ®Google Scholar

Yugawa K, Itoh S, Yoshizumi T, et al. CMTM6 stabilizes PD-L1 expression and is a new prognostic impact factor in Hepatocellular Carcinoma. Hepatol Commun. 2021;5(2):334–348. doi:10.1002/hep4.1643

 PubMed Web of Science ®Google Scholar