Synergistic Anticancer Strategy Targeting ECM Stiffness: Integration of Matrix Softening and Mechanical Signal Transduction Blockade in Primary Liver Cancers.

Autor: Shen Z; Zhejiang Key Laboratory of Multi-omics Precision Diagnosis and Treatment of Liver Diseases, Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310016, China.; Zhejiang Minimal Invasive Diagnosis and Treatment Technology Research Center of Severe Hepatobiliary Disease, Zhejiang Research and Development Engineering Laboratory of Minimally Invasive Technology and Equipment, Hangzhou, Zhejiang, 310016, China.; Zhejiang University Cancer Center, Hangzhou, Zhejiang, 310058, China.; Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, Zhejiang, 311121, China., Tao L; Zhejiang Key Laboratory of Multi-omics Precision Diagnosis and Treatment of Liver Diseases, Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310016, China.; Zhejiang Minimal Invasive Diagnosis and Treatment Technology Research Center of Severe Hepatobiliary Disease, Zhejiang Research and Development Engineering Laboratory of Minimally Invasive Technology and Equipment, Hangzhou, Zhejiang, 310016, China.; Zhejiang University Cancer Center, Hangzhou, Zhejiang, 310058, China.; Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, Zhejiang, 311121, China., Wang Y; Zhejiang Key Laboratory of Multi-omics Precision Diagnosis and Treatment of Liver Diseases, Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310016, China.; Zhejiang Minimal Invasive Diagnosis and Treatment Technology Research Center of Severe Hepatobiliary Disease, Zhejiang Research and Development Engineering Laboratory of Minimally Invasive Technology and Equipment, Hangzhou, Zhejiang, 310016, China.; Zhejiang University Cancer Center, Hangzhou, Zhejiang, 310058, China.; Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, Zhejiang, 311121, China., Zhu Y; Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310016, China., Pan H; Zhejiang Key Laboratory of Multi-omics Precision Diagnosis and Treatment of Liver Diseases, Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310016, China.; Zhejiang Minimal Invasive Diagnosis and Treatment Technology Research Center of Severe Hepatobiliary Disease, Zhejiang Research and Development Engineering Laboratory of Minimally Invasive Technology and Equipment, Hangzhou, Zhejiang, 310016, China.; Zhejiang University Cancer Center, Hangzhou, Zhejiang, 310058, China.; Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, Zhejiang, 311121, China., Li Y; Department of Orthopaedic Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China., Jiang S; Department of Thyroid and Breast Surgery, Ningbo First Hospital, Zhejiang University, Ningbo, Zhejiang, 315010, China., Zheng J; Zhejiang Key Laboratory of Multi-omics Precision Diagnosis and Treatment of Liver Diseases, Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310016, China.; Zhejiang Minimal Invasive Diagnosis and Treatment Technology Research Center of Severe Hepatobiliary Disease, Zhejiang Research and Development Engineering Laboratory of Minimally Invasive Technology and Equipment, Hangzhou, Zhejiang, 310016, China.; Zhejiang University Cancer Center, Hangzhou, Zhejiang, 310058, China.; Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, Zhejiang, 311121, China., Cai J; Zhejiang Key Laboratory of Multi-omics Precision Diagnosis and Treatment of Liver Diseases, Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310016, China.; Zhejiang Minimal Invasive Diagnosis and Treatment Technology Research Center of Severe Hepatobiliary Disease, Zhejiang Research and Development Engineering Laboratory of Minimally Invasive Technology and Equipment, Hangzhou, Zhejiang, 310016, China.; Zhejiang University Cancer Center, Hangzhou, Zhejiang, 310058, China.; Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, Zhejiang, 311121, China., Liu Y; Zhejiang Key Laboratory of Multi-omics Precision Diagnosis and Treatment of Liver Diseases, Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310016, China.; Zhejiang Minimal Invasive Diagnosis and Treatment Technology Research Center of Severe Hepatobiliary Disease, Zhejiang Research and Development Engineering Laboratory of Minimally Invasive Technology and Equipment, Hangzhou, Zhejiang, 310016, China.; Zhejiang University Cancer Center, Hangzhou, Zhejiang, 310058, China.; Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, Zhejiang, 311121, China., Lin K; Zhejiang Key Laboratory of Multi-omics Precision Diagnosis and Treatment of Liver Diseases, Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310016, China.; Zhejiang Minimal Invasive Diagnosis and Treatment Technology Research Center of Severe Hepatobiliary Disease, Zhejiang Research and Development Engineering Laboratory of Minimally Invasive Technology and Equipment, Hangzhou, Zhejiang, 310016, China.; Zhejiang University Cancer Center, Hangzhou, Zhejiang, 310058, China.; Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, Zhejiang, 311121, China., Li S; Zhejiang Key Laboratory of Multi-omics Precision Diagnosis and Treatment of Liver Diseases, Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310016, China.; Zhejiang Minimal Invasive Diagnosis and Treatment Technology Research Center of Severe Hepatobiliary Disease, Zhejiang Research and Development Engineering Laboratory of Minimally Invasive Technology and Equipment, Hangzhou, Zhejiang, 310016, China.; Zhejiang University Cancer Center, Hangzhou, Zhejiang, 310058, China.; Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, Zhejiang, 311121, China., Tong Y; Zhejiang Key Laboratory of Multi-omics Precision Diagnosis and Treatment of Liver Diseases, Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310016, China.; Zhejiang Minimal Invasive Diagnosis and Treatment Technology Research Center of Severe Hepatobiliary Disease, Zhejiang Research and Development Engineering Laboratory of Minimally Invasive Technology and Equipment, Hangzhou, Zhejiang, 310016, China.; Zhejiang University Cancer Center, Hangzhou, Zhejiang, 310058, China.; Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, Zhejiang, 311121, China., Shangguan L; Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310016, China., Xu J; Zhejiang Key Laboratory of Multi-omics Precision Diagnosis and Treatment of Liver Diseases, Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310016, China.; Zhejiang Minimal Invasive Diagnosis and Treatment Technology Research Center of Severe Hepatobiliary Disease, Zhejiang Research and Development Engineering Laboratory of Minimally Invasive Technology and Equipment, Hangzhou, Zhejiang, 310016, China.; Zhejiang University Cancer Center, Hangzhou, Zhejiang, 310058, China.; Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, Zhejiang, 311121, China., Liang X; Zhejiang Key Laboratory of Multi-omics Precision Diagnosis and Treatment of Liver Diseases, Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310016, China.; Zhejiang Minimal Invasive Diagnosis and Treatment Technology Research Center of Severe Hepatobiliary Disease, Zhejiang Research and Development Engineering Laboratory of Minimally Invasive Technology and Equipment, Hangzhou, Zhejiang, 310016, China.; Zhejiang University Cancer Center, Hangzhou, Zhejiang, 310058, China.; Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, Zhejiang, 311121, China.; School of Medicine, Shaoxing University, Shaoxing, Zhejiang, 312000, China.
Jazyk: angličtina
Zdroj: Advanced science (Weinheim, Baden-Wurttemberg, Germany) [Adv Sci (Weinh)] 2024 Dec 20, pp. e2403040. Date of Electronic Publication: 2024 Dec 20.
DOI: 10.1002/advs.202403040
Abstrakt: The development of primary liver cancer (hepatocellular carcinoma [HCC] and intrahepatic cholangiocarcinoma [ICC]) is linked to its physical microenvironment, particularly extracellular matrix (ECM) stiffness. Potential anticancer strategies targeting ECM stiffness include prevention/reversal of the stiffening process and disruption of the response of cancer cells to mechanical signals from ECM. However, each strategy has limitations. Therefore, the authors propose integrating them to maximize their strengths. Compared with HCC, ICC has a stiffer ECM and a worse prognosis. Therefore, ICC is selected to investigate mechanisms underlying the influence of ECM stiffness on cancer progression and application of the integrated anticancer strategy targeting ECM stiffness. In summary, immunofluorescence results for 181 primary liver cancer tissue chips (ICC, n = 91; HCC, n = 90) and analysis of TCGA mRNA-sequencing demonstrate that ECM stiffness can affect phenotypes of primary liver cancers. The YAP1/ABHD11-AS1/STAU2/ZYX/p-YAP1 pathway is a useful entry point for exploration of specific mechanisms of mechanical signal conduction from the ECM in ICC cells and their impact on cancer progression. Moreover, a synergistic anticancer strategy targeting ECM stiffness (ICCM@NPs + siABHD11-AS1@BAPN) is constructed by integrating ECM softening and blocking intracellular mechanical signal transduction in ICC and can provide insights for the treatment of cancers characterized by stiff ECM.
(© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)
Databáze: MEDLINE
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