PCTAIRE1-knockdown sensitizes cancer cells to TNF family cytokines

PloS One
Teruki YanagiShu-ichi Matsuzawa

Abstract

While PCTAIRE1/PCTK1/Cdk16 is overexpressed in malignant cells and is crucial in tumorigenesis, its function in apoptosis remains unclear. Here we investigated the role of PCTAIRE1 in apoptosis, especially in the extrinsic cell death pathway. Gene-knockdown of PCTAIRE1 sensitized prostate cancer PPC1 and Du145 cells, and breast cancer MDA-MB-468 cells to TNF-family cytokines, including TNF-related apoptosis-inducing ligand (TRAIL). Meanwhile, PCTAIRE1-knockdown did not sensitize non-malignant cells, including diploid fibroblasts IMR-90 and the immortalized prostate epithelial cell line 267B1. PCTAIRE1-knockdown did not up-regulate death receptor expression on the cell surface or affect caspase-8, FADD and FLIP expression levels. PCTAIRE1-knockdown did promote caspase-8 cleavage and RIPK1 degradation, while RIPK1 mRNA knockdown sensitized PPC1 cells to TNF-family cytokines. Furthermore, the kinase inhibitor SNS-032, which inhibits PCTAIRE1 kinase activity, sensitized PPC1 cells to TRAIL-induced apoptosis. Together these results suggest that PCTAIRE1 contributes to the resistance of cancer cell lines to apoptosis induced by TNF-family cytokines, which implies that PCTAIRE1 inhibitors could have synergistic effects with TNF-family...Continue Reading

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Citations

Jun 29, 2016·Molecular Therapy. Nucleic Acids·Teruki YanagiShu-Ichi Matsuzawa
Dec 17, 2016·International Journal of Molecular Sciences·Jung-Chun LinYing-Ju Lin
Apr 14, 2017·Cancer Investigation·Qi Zhou
Sep 4, 2019·Journal of Cellular Biochemistry·Muhammad Imran QadirMajid Manzoor
Feb 7, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Osama GarwainSuzanne Scarlata
Apr 10, 2018·Frontiers in Oncology·Teruki YanagiHiroo Hata
Jul 19, 2017·Journal of Experimental & Clinical Cancer Research : CR·Yitao WangZhisu Liu
Mar 19, 2020·International Journal of Molecular Sciences·Lei DingQinghua Cui

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Methods Mentioned

BETA
transfection
flow cytometry
protein assay
immunoprecipitation
FACS
two hybrid

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