The depletion of ATM inhibits colon cancer proliferation and migration via B56γ2-mediated Chk1/p53/CD44 cascades
作者： Rui Liu , Jiajia Tang , Chaodong Ding , Weicheng Liang , Li Zhang
DOI: 10.1016/J.CANLET.2016.12.040
关键词:
摘要: Ataxia-telangiectasia mutated (ATM) protein kinase is a major guardian of genomic stability, and its well-established function in cancer tumor suppression. Here, we report an oncogenic role ATM. Using two isogenic sets human colon cell lines that differed only their ATM status, demonstrated deficiency significantly inhibits proliferation, migration, invasion. The tumor-suppressive depletion not modulated by the compensatory activation ATR, but it associated with B56γ2-mediated Chk1/p53/CD44 signaling pathways. Under normal growth conditions, prevents B56γ2 ubiquitination degradation, which activates PP2A-mediated Chk1/p53/p21 pathways, leading to senescence cycle arrest. CD44 was validated as novel target based on ability rescue migration invasion defects ATM-depleted cells. p53 induced suppresses transcription, thus resulting epithelial-mesenchymal transition (EMT) Our study suggests has tumorigenic potential post-formed neoplasia, supports appealing for improving therapy.
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