SPOP promotes CREB5 ubiquitination to inhibit MET signaling in liver cancer.

Autor: Gong DA; Key Laboratory of Molecular Biology for Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China., Zhou P; Key Laboratory of Molecular Biology for Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China., Chang WY; Key Laboratory of Molecular Biology for Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China., Yang JY; Key Laboratory of Molecular Biology for Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China., Zhang YL; Key Laboratory of Molecular Biology for Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China., Huang AL; Key Laboratory of Molecular Biology for Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China., Tang N; Key Laboratory of Molecular Biology for Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China. Electronic address: nitang@cqmu.edu.cn., Wang K; Key Laboratory of Molecular Biology for Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China. Electronic address: wangkai@cqmu.edu.cn.
Jazyk: angličtina
Zdroj: Biochimica et biophysica acta. Molecular cell research [Biochim Biophys Acta Mol Cell Res] 2024 Feb; Vol. 1871 (2), pp. 119642. Date of Electronic Publication: 2023 Nov 22.
DOI: 10.1016/j.bbamcr.2023.119642
Abstrakt: 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 cullin-RING 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 SPOP-CREB5 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.
Competing Interests: Declaration of competing interest The authors declare that there are no potential conflicts of interest.
(Copyright © 2023. Published by Elsevier B.V.)
Databáze: MEDLINE
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