GJB2 Promotes HCC Progression by Activating Glycolysis Through Cytoplasmic Translocation and Generating a Suppressive Tumor Microenvironment Based on Single Cell RNA Sequencing.

Autor: Liu H; Department of General Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210000, China.; Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key laboratory of Hepatobiliary cancers, Nanjing Medical University, Nanjing, 210000, China., Li X; Department of General Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210000, China., Zhang C; Department of General Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210000, China., Hao X; Department of Hepatobiliopancreatic Surgery, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450000, China., Cao Y; Department of General Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210000, China., Wang Y; Department of Immunology, Key Laboratory of Immune Microenvironment and Diseases, NHC Key Laboratory of Antibody Technique, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Personalized Cancer Medicine, Nanjing Medical University, Nanjing, 210000, China., Zhuang H; Department of Hepatobiliopancreatic Surgery, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450000, China., Yu N; Department of Pharmaceutical Preparation, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004, China., Huang T; Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key laboratory of Hepatobiliary cancers, Nanjing Medical University, Nanjing, 210000, China., Liu C; Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key laboratory of Hepatobiliary cancers, Nanjing Medical University, Nanjing, 210000, China., Cao H; Department of General Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210000, China., Lu Z; Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key laboratory of Hepatobiliary cancers, Nanjing Medical University, Nanjing, 210000, China., Song J; Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key laboratory of Hepatobiliary cancers, Nanjing Medical University, Nanjing, 210000, China., Liu L; First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.; National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, 301619, China., Wang H; Department of General Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210000, China., Li Z; Department of plastics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China., Tang W; Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key laboratory of Hepatobiliary cancers, Nanjing Medical University, Nanjing, 210000, China.
Jazyk: angličtina
Zdroj: Advanced science (Weinheim, Baden-Wurttemberg, Germany) [Adv Sci (Weinh)] 2024 Oct; Vol. 11 (39), pp. e2402115. Date of Electronic Publication: 2024 Aug 20.
DOI: 10.1002/advs.202402115
Abstrakt: Despite substantial breakthroughs in the treatment of hepatocellular carcinoma (HCC) in recent years, many patients are diagnosed in the middle or late stages, denying them the option for surgical excision. Therefore, it is of great importance to find effective therapeutic targets of HCC. In this study, it is found that Gap junction protein beta-2 (GJB2) is highly enriched in malignant cells based on single-cell RNA sequencing and higher expression of GJB2 indicates a worse prognosis. The localization of GJB2 in HCC cancer cells is changed compared with normal liver tissue. In cancer cells, GJB2 tends to be located in the cytoplasm and nucleus, while in normal tissues, GJB2 is mainly located on the cell membrane. GJB2 is related to glycolysis, promoting NF-κB pathway via inducing the ubiquitination degradation of IκBa, and activating HIF-1α/GLUT-1/PD-L1 pathway. In addition, GJB2 knockdown reshapes tumor immune microenvironment and Salvianolic acid B inhibits the activity of GJB2. In conclusion, GJB2 promotes HCC progression by activating glycolysis through cytoplasmic translocation and generating a suppressive tumor microenvironment. Salvianolic acid B inhibits the expression of GJB2 and enhances the sensitivity of anti-PD1 therapy, which may provide insights into the development of novel combination therapeutic strategies for HCC.
(© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)
Databáze: MEDLINE
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