Academic Journal
Mechanosensors Collaborate to Regulate DNA Damage Repair in Hepatocellular Carcinoma.
| Τίτλος: | Mechanosensors Collaborate to Regulate DNA Damage Repair in Hepatocellular Carcinoma. |
|---|---|
| Συγγραφείς: | Li J; Liver Cancer Institute, Zhongshan Hospital, Fudan University & Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, PR China.; Department of Gastroenterology, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, PR China., Ren Z; Liver Cancer Institute, Zhongshan Hospital, Fudan University & Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, PR China., Yao J; Liver Cancer Institute, Zhongshan Hospital, Fudan University & Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, PR China., Zhao Y; Liver Cancer Institute, Zhongshan Hospital, Fudan University & Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, PR China., Xu Y; Liver Cancer Institute, Zhongshan Hospital, Fudan University & Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, PR China., Yu H; Liver Cancer Institute, Zhongshan Hospital, Fudan University & Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, PR China., Huang C; Department of Endocrinology, Huashan Hospital, Fudan University, Shanghai, PR China., Wang M; Liver Cancer Institute, Zhongshan Hospital, Fudan University & Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, PR China., Yao F; Liver Cancer Institute, Zhongshan Hospital, Fudan University & Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, PR China., Li M; Liver Cancer Institute, Zhongshan Hospital, Fudan University & Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, PR China., Wang Y; Department of Radiology, Shanghai Cancer Center, Fudan University, Shanghai, PR China., Gao D; Liver Cancer Institute, Zhongshan Hospital, Fudan University & Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, PR China., Zhao Y; Liver Cancer Institute, Zhongshan Hospital, Fudan University & Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, PR China., Liu B; Liver Cancer Institute, Zhongshan Hospital, Fudan University & Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, PR China., Wang Z; Department of Oncology, Zhongshan Hospital, Fudan University, Shanghai, PR China., Dong Y; Department of Radiation Oncology, The Affiliated Hospital of Qingdao University, Qingdao, PR China., Chen R; Liver Cancer Institute, Zhongshan Hospital, Fudan University & Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, PR China., Cui J; Liver Cancer Institute, Zhongshan Hospital, Fudan University & Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, PR China. |
| Πηγή: | Cancer research [Cancer Res] 2026 Oct 15; Vol. 86 (20), pp. 5043-5062. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: American Association for Cancer Research Country of Publication: United States NLM ID: 2984705R Publication Model: Print Cited Medium: Internet ISSN: 1538-7445 (Electronic) Linking ISSN: 00085472 NLM ISO Abbreviation: Cancer Res Subsets: MEDLINE |
| Imprint Name(s): | Publication: Baltimore, Md. : American Association for Cancer Research Original Publication: Chicago [etc.] |
| Ιατρικοί όροι (MeSH): | Carcinoma, Hepatocellular*/genetics , Carcinoma, Hepatocellular*/metabolism , Carcinoma, Hepatocellular*/pathology , Liver Neoplasms*/genetics , Liver Neoplasms*/metabolism , Liver Neoplasms*/pathology , DNA Repair* , DNA Damage* , Mechanotransduction, Cellular*, Nuclear Proteins/metabolism ; DNA-Binding Proteins/metabolism ; Protein Phosphatase 2/metabolism ; Cell Cycle Proteins/metabolism ; Humans ; Cell Line, Tumor ; Phosphorylation ; MRE11 Homologue Protein |
| Περίληψη: | Increased matrix stiffness is a biomechanical feature of hepatocellular carcinoma (HCC) that functions as an important promoting factor driving tumor progression. Characterization of the mechanosensors and the underlying downstream mechanisms driving HCC could help identify potential treatment strategies. In this study, we developed a standard procedure for screening and identifying mechanosensors, revealing two HCC mechanosensors, SDC4 and PKD2. These two mechanosensory pathways collaboratively mediated matrix stiffness-promoted DNA damage repair (DDR). Specifically, SDC4 and PKD2 modulated matrix stiffness-increased BANF1 nuclear translocation by increasing protein phosphatase 2A assembly and activity. Subsequently, nuclear BANF1 boosted the formation of the MRE11-RAD50-NBS1 complex and phosphorylation of its downstream effectors to enhance DDR. These findings not only expand the theoretical understanding of matrix stiffness-regulated DDR but also offer a screening/identification approach for mechanosensors in cancer. Significance: Matrix stiffness enhances DNA repair via dual pathways in hepatocellular carcinoma, suggesting that targeting mechanosensory cross-talk could be a potential strategy to overcome cytotoxic drug resistance. (©2026 The Authors; Published by the American Association for Cancer Research.) |
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| Grant Information: | 82473492 National Natural Science Foundation of China (NSFC) |
| Substance Nomenclature: | 0 (Nuclear Proteins) 0 (DNA-Binding Proteins) EC 3.1.3.16 (Protein Phosphatase 2) 0 (NBN protein, human) 0 (Cell Cycle Proteins) EC 3.1.- (MRE11 Homologue Protein) 0 (MRE11 protein, human) |
| Entry Date(s): | Date Created: 20260729 Date Completed: 20261015 Latest Revision: 20261017 |
| Update Code: | 20261017 |
| PubMed Central ID: | PMC13669727 |
| DOI: | 10.1158/0008-5472.CAN-25-4356 |
| PMID: | 42525956 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1538-7445 |
|---|---|
| DOI: | 10.1158/0008-5472.CAN-25-4356 |