期刊
JOURNAL OF CELLULAR PHYSIOLOGY
卷 234, 期 7, 页码 11871-11881出版社
WILEY
DOI: 10.1002/jcp.27824
关键词
colorectal cancer; CtIP; drug sensitivity; etoposide; G2; M phase arrest; p53
资金
- National Natural Science Foundation of China [81670095]
- China Postdoctoral Science Foundation [2018M630313, 2018T110239]
- Science and Technology development Program of Jilin Province [20180520104JH]
Acquired resistance to cytotoxic antineoplastic agents is a major clinical challenge in tumor therapy; however, the mechanisms involved are still poorly understood. In this study, we show that knockdown of CtIP, a corepressor of CtBP, promotes cell proliferation and alleviates G2/M phase arrest in etoposide (Eto)-treated HCT116 cells. Although the expression of p21 and growth arrest and DNA damage inducible (GADD45a), which are important targets of p53, was downregulated in CtIP-deficient HCT116 cells, p53 deletion did not affect G2/M arrest after Eto treatment. In addition, the phosphorylation levels of Ser317 and Ser345 in Chk1 and of Ser216 in CDC25C were lower in CtIP-deficient HCT116 cells than in control cells after Eto treatment. Our results indicate that CtIP may enhance cell sensitivity to Eto by promoting G2/M phase arrest, mainly through the ATR-Chk1-CDC25C pathway rather than the p53-p21/GADD45a pathway. The expression of CtIP may be a useful biomarker for predicting the drug sensitivity of colorectal cancer cells.
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