SPOP promotes CREB5 ubiquitination to inhibit MET signaling in liver cancer
作者全名："Gong, De-ao; Zhou, Peng; Chang, Wen-yi; Yang, Jia-yao; Zhang, Yan-lai; Huang, Ai-long; Tang, Ni; Wang, Kai"
作者地址："[Gong, De-ao; Zhou, Peng; Chang, Wen-yi; Yang, Jia-yao; Zhang, Yan-lai; Huang, Ai-long; Tang, Ni; Wang, Kai] Chongqing Med Univ, Affiliated Hosp 2, Inst Viral Hepatitis, Dept Infect Dis,Key Lab Mol Biol Infect Dis Minist, Chongqing 400016, Peoples R China"
通信作者："Tang, N; Wang, K (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Inst Viral Hepatitis, Dept Infect Dis,Key Lab Mol Biol Infect Dis Minist, Chongqing 400016, Peoples R China."
来源：BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
ESI学科分类：MOLECULAR BIOLOGY & GENETICS
WOS号：WOS:001125093100001
JCR分区：Q2
影响因子：5.1
年份：2024
卷号：1871
期号：2
开始页：
结束页：
文献类型：Article; Early Access
关键词：Liver cancer; SPOP; Ubiquitination; CREB5; MET
摘要："Liver cancer is ranked as the sixth most prevalent from of malignancy globally and stands as the third primary contributor to cancer-related mortality. Metastasis is the main reason for liver cancer treatment failure and patient deaths. Speckle-type POZ protein (SPOP) serves as a crucial substrate junction protein within the cullinRING E3 ligase complex, acting as a significant tumor suppressor in liver cancer. Nevertheless, the precise molecular mechanism underlying the role of SPOP in liver cancer metastasis remain elusive. In the current study, we identified cAMP response element binding 5 (CREB5) as a novel SPOP substrate in liver cancer. SPOP facilitates non-degradative K63-polyubiquitination of CREB5 on K432 site, consequently hindering its capacity to activate receptor tyrosine kinase MET. Moreover, liver cancer-associated SPOP mutant S119N disrupts the SPOPCREB5 interactions and impairs the ubiquitination of CREB5.This disruption ultimately leads to the activation of the MET signaling pathway and enhances metastatic properties of hepatoma cells both in vitro and in vivo. In conclusion, our findings highlight the functional significance of the SPOP-CREB5-MET axis in liver cancer metastasis."
基金机构："National Natural Science Foundation of China [82273238, 82272975, U20A20392]; Project 111 [D20028]; Chongqing Medical Scientific Research Project (Joint project of Chongqing Health Commission and Science and Technology Bureau) [2023DBXM007]; Innovative and Entrepreneurial Team of Chongqing Talents Plan, Senior Medical Talents Program of Chongqing for Young and Middlaged, Program for Youth Innovation in Future Medicine, Chongqing Medical University [W0101, W0036]; Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical University"
基金资助正文："This study was supported by the National Natural Science Foundation of China (82273238, KW; 82272975, NT; U20A20392, ALH) , the 111 Project (No. D20028, AH) , Chongqing Medical Scientific Research Project (Joint project of Chongqing Health Commission and Science and Technology Bureau, 2023DBXM007, NT) , the Innovative and Entrepreneurial Team of Chongqing Talents Plan, Senior Medical Talents Program of Chongqing for Young and Middleaged, Program for Youth Innovation in Future Medicine, Chongqing Medical University (W0101, KW; W0036, NT) , Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical University."
