1. Academic Validation
  2. Semaphorin 4C promotes motility and immunosuppressive activity of cancer cells via CRMP3 and PD-L1

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

  • Am J Cancer Res. 2022 Feb 15;12(2):713-728.
Yu-Hsuan Hung 1 Ming-Derg Lai 2 Wen-Chun Hung 1 Li-Tzong Chen 1 3 4
Affiliations

Affiliations

  • 1 National Institute of Cancer Research, National Health Research Institutes Tainan 704, Taiwan.
  • 2 Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University Tainan 704, Taiwan.
  • 3 Division of Hematology & Oncology, Department of Internal Medicine, College of Medicine, Kaohsiung Medical University Kaohsiung 807, Taiwan.
  • 4 Department of Medical Research, Kaohsiung Medical University Hospital Kaohsiung 807, Taiwan.
PMID: 35261797
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 interacted 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.

Keywords

CRMP3; PD-L1; SEMA4C; colon cancer.

Figures
Products