Epigenetic Activation of TWIST1 by MTDH Promotes Cancer Stem–like Cell Traits in Breast Cancer
作者： Yajun Liang , Jing Hu , Jiatao Li , Yingjie Liu , Jingyi Yu
DOI: 10.1158/0008-5472.CAN-15-0930
关键词:
摘要: Cancer stem-like cells (CSC) are a cell subpopulation that can reinitiate tumors, resist chemotherapy, and give rise to metastases. Metadherin (MTDH) contributes widely tumor growth, drug resistance, relapse, metastasis, but its molecular mechanisms of action not well understood. Here, we report MTDH drives CSC expansion by promoting the expression TWIST1, transcription factor critical for cancer stemness metastasis. activates TWIST1 indirectly facilitating histone H3 acetylation on promoter, process mediated acetyltransferase CBP. Mechanistic investigations showed interacts with CBP prevents ubiquitin-mediated degradation, licensing transcriptional activation TWIST1. In clinical specimens breast cancer, correlates positively abundance. Overall, our work revealed promotes accumulation tumorigenicity regulating deepening understanding function in cancer.
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