Semaphorin 4C promotes motility and immunosuppressive activity of cancer cells via CRMP3 and PD-L1

xlomafota13 shared this article with you from Inoreader Semaphorin 4C promotes motility and immunosuppressive activity of cancer cells via CRMP3 and PD-L1 Via American Journal of Cancer Research Am J Cancer Res. 2022 Feb 15;12(2):713-728. eCollection 2022. ABSTRACT Semaphorins (SEMAs) are membrane-bound or soluble proteins that participate in organ development and cancer progression, however, the detailed role of SEMAs in carcinogenesis is not fully elucidated yet. Our in silico analysis showed among the differentially expressed SEMAs in colon cancer tissues, patients with higher SEMA4C expression tumors had worse survival. The migration and invasion of the HCT116 and CT26 colon cancer cells were significantly suppressed by SEMA4C neutralizing antibody treatment; while enhanced by ectopic expression of SEMA4C. Subsequently, RNA sequencing study revealed microtubule polymerization- and nucleation-related genes are highly enriched in SEMA4C overexpression HCT116 cells. Western blotting showed the negative correlation between the levels of SEMA4C expression and tubulin acetylation. Mechanistic study showed SEMA4C interacte d with and stabilized collapsin response mediator protein 3 (CRMP3), a novel deacetylase, to increase α-tubulin deacetylation and cell motility, which could be effectively attenuated after HDAC inhibitors treatment. We also found that a tumor-suppressive miRNA let-7b can target SEMA4C and act synergistically with SEMA4C neutralizing antibody to suppress the motility of colon cancer cells. In addition, blockade of SEMA4C could attenuate the expression of program death ligand 1 (PD-L1). Collectively, our results highlight that SEMA4C may promote colon cancer progression through modulating CRMP3-mediated tubulin deacetylation and PD-L1-mediated immunosuppression. PMID:35261797 | PMC:PMC8899990 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.