EZH2 is regulated by ERK/AKT and targets integrin alpha2 gene to control Epithelial–Mesenchymal Transition and anoikis in colon cancer cells

摘要: Epithelial-Mesenchymal Transition is a good example of cell plasticity. In tumorigenesis, this process has been associated with metastasis. Overexpression EZH2 detected in most malignant human tumors, including colorectal carcinomas. Herein, we provide evidence supporting the idea that oncogenic colon cancer models partially controlled by epigenetic factors such as transcription regulator EZH2. Evaluation mRNA and protein levels revealed overexpression lines metastatic traits. Analysis expression was expanded clinical samples cancer, high level correlates appearance Furthermore, inhibition ERK AKT pathways attenuates overexpression. promoter analysis illustrates presence putative AP-1 binding sites occupancy FRA-1 C-JUN demonstrated here on promoter. Abrogation impairs ability cells to move anoikis three-dimensional environment. Integrin alpha2 identified be novel target chromatin immunoprecipitation short hairpin RNA analysis. This study proposes activation ERK/AKT FRA1/C-JUN induce overexpression, which results silencing. Our show how deregulation mechanisms can affect aggressiveness propose potential metastasis marker and/or therapeutic for treatment.