SREBP2-activated CNPY3 Phase Separation Promotes Colorectal Cancer by Enhancing MDM2-mediated p53 Degradation
Li Xue, Min-Yue Yin, Yanfei Wei, Jie Xing, Qian Zhang, Ye Zong, Zhang Shu-tian, Si-An Xie
University of Electronic Science and Technology of China Capital Medical University National Clinical Research Center for Digestive Diseases Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital
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. Our work unveils a SREBP2-CNPY3-MDM2-p53 signaling axis that links cholesterol metabolic dysregulation to p53 pathway inactivation in CRC. We further established that the oncogenic activity of CNPY3 is mediated through its biophysical property of LLPS. These findings nominate CNPY3 as a novel prognostic biomarker and a compelling therapeutic target for p53-wild-type CRC.
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