IL-13/IL-13RA2 signaling promotes colorectal cancer stem cell tumorigenesis by inducing ubiquitinated degradation of p53

作     者：Baoyu He Jing Liang Qianqian Qin Yuqin Zhang Shuo Shi Jinghe Cao Zhixin Zhang Qingli Bie Rou Zhao Li Wei Baogui Zhang Bin Zhang Baoyu He;Jing Liang;Qianqian Qin;Yuqin Zhang;Shuo Shi;Jinghe Cao;Zhixin Zhang;Qingli Bie;Rou Zhao;Li Wei;Baogui Zhang;Bin Zhang

作者机构：Department of Laboratory MedicineAffiliated Hospital of Jining Medical UniversityJining Medical UniversityJiningShandong 272000China Postdoctoral Mobile Station of Shandong University of Traditional Chinese MedicineJinanShandong 250355China Department of Reproductive MedicineAffiliated Hospital of Jining Medical UniversityJining Medical UniversityJiningShandong 272000China Department of Gastrointestinal SurgeryAffiliated Hospital of Jining Medical UniversityJining Medical UniversityJiningShandong 272000China Institute of Forensic Medicine and Laboratory MedicineJining Medical UniversityJiningShandong 272067China 

出 版 物：《Genes & Diseases》 (基因与疾病（英文）)

年 卷 期：2024年第11卷第1期

页      面：495-508页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China(No.82173371,82273447,82273069) the project funded by China Postdoctoral Science Foundation(No.2022M711320,2022M711322) Shandong Postdoctoral innovation project(China)(No.SDCX-ZG202201002) Tai Shan Young Scholar Foundation of Shandong Province,China(No.tsqn201909192) Shandong Provincial Natural Science Foundation(China)(No.ZR2020YQ59,ZR2021QH021,ZR202112020099) Youth Innovation Science and Technology Support Plan of Shandong Province’s colleges and universities(China)(No.2021KJ017) the Project of Medicine Health and Technology Development Plan of Shandong Province,China(No.202103030586 and 202103030411) the Miaopu Research of the Affiliated Hospital of Jining Medical University,Shandong,China(No.MP-ZD-2020-005 and MP-ZD-2021-001) Ph.D.Research Foundation of the Affiliated Hospital of Jining Medical University,Shandong,China(No.2022-BS003) Research Fund for Lin He’s Academician Workstation of New Medicine and Clinical Translation in Jining Medical University,Shandong,China(No.JYHL2022FZD04) 

主　　题：Autophagy Colorectal cancer stem cells IL-13/IL-13RA2 signaling p53 

摘      要：Cancer stem cells(CSCs)are considered tumor-initiating cells and the main drivers of disease *** these rare cancer cells,however,remains challenging with respect to therapeutic ***,we report the up-regulation of IL-13RA2 expression in colorectal cancer(CRC)tissues and spheroid *** expression of IL-13RA2 was positively correlated with canonical stemness markers in *** further demonstrated that the level of IL-13 was up-regulated in the serum of CRC ***,recombinant IL-13(rIL13)stimulation promoted the sphere formation,proliferation,and migration of CRC cells in vitro and enhanced tumorigenesis in *** phenotype could be reversed by knocking down ***,IL-13 activated autophagy by inducing LC3I/LC3II transformation in CRC-CSCs,which was crucial for the biological functions of *** further demonstrated that IL-13RA2 acted as a modular link of the E3 ligase UBE3C and the substrate p53 protein,enhancing the interaction of UBE3C and p53,thereby inducing the K48-linked ubiquitination of *** conclusion,the IL-13/IL-13RA2 signaling cascade promotes CRC-CSC self-renewal and tumorigenesis by inducing p53 ubiquitination,adding an important layer to the connection between IL-13 and p53,which can be translated into novel targeted therapies.