CtIP promotes G2/M arrest in etoposide-treated HCT116 cells in a p53-independent manner |
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| Authors: | Hongyu Chen Jin Shan Dandan Chen Ruoxi Wang Wenjing Qi Hailong Wang Yueshuang Ke Wenguang Liu Xianlu Zeng |
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| Institution: | 1. The Key Laboratory of Molecular Epigenetics of Ministry of Education, Institute of Genetics and Cytology, Northeast Normal University, Changchun, China;2. Laboratory of Noncoding RNA, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China;3. The Key Laboratory of Molecular Epigenetics of Ministry of Education, Institute of Genetics and Cytology, Northeast Normal University, Changchun, China
Department of Bioscience, Changchun Normal University, Changchun, China;4. College of Life Science and Beijing Key Laboratory of DNA Damage Response, Capital Normal University, Beijing, China |
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| Abstract: | 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 α (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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| Keywords: | colorectal cancer CtIP drug sensitivity etoposide G2/M phase arrest p53 |
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