The Molecular Mechanism of STAT3 Signal Transduction Induced by TNFα

CAO Ting^1,2, ZHANG Zhao^1,2, HU Ling^1,2, JIANG Binyuan^1,2, HU Jinyue^1,2*

(¹The Department of Clinical Laboratory Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha 410004, China; ²Central Laboratory, Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha 410004, China)

Abstract:

This study explored the molecular mechanism of STAT3 signal transduction induced by TNFα (tumor necrosis factor α). FACS was employed to determine the expression of TNF receptor TNFR1 in 5-8F nasopharyngeal carcinoma cells and HeLa cervical cancer cells. qRT-PCR was used to measure the mRNA levels of TNFR1 and TNFR2 induced by TNFα. ELISA was used to measure the protein levels of cytokine IL-8. Western blot was used to detect the total and phosphorylated protein levels of receptors and signal molecules. The results showed that 5-8F and HeLa cells expressed functional TNF receptor and EGFR. The treatment of cells with TNFα induced the activation of STAT3 in a time-dependent and dose-dependent manner. TNFα could also activate EGFR. Treatment with EGFR inhibitors reversed the phosphorylation of EGFR (Y1068) induced by TNFα and also reversed the phosphorylation of STAT3. Furthermore, TNFα activated the pro-cancer tyrosine protein kinase SRC. After treatment with SRC inhibitors, TNFα-induced EGFR activation and downstream STAT3 phosphorylation were reversed. In conclusion, in certain cancer cells, the signal transduction pathway TNFα-SRC-EGFR-STAT3 is existed, and EGFR may be a bridge for linking inflammation with cancer.

CSTR: 32200.14.cjcb.2022.02.0002