1. Academic Validation
  2. Targeting extracellular matrix stiffness and mechanotransducers to improve cancer therapy

Targeting extracellular matrix stiffness and mechanotransducers to improve cancer therapy

  • J Hematol Oncol. 2022 Mar 24;15(1):34. doi: 10.1186/s13045-022-01252-0.
Yangfu Jiang 1 Hongying Zhang 2 Jiao Wang 3 Yongliang Liu 2 Ting Luo 4 Hui Hua 5
Affiliations

Affiliations

  • 1 Laboratory of Oncogene, State Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China. jyangfu@scu.edu.cn.
  • 2 Laboratory of Oncogene, State Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.
  • 3 School of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
  • 4 Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
  • 5 Laboratory of Stem Cell Biology, West China Hospital, Sichuan University, Chengdu, China. huahuihx@scu.edu.cn.
Abstract

Cancer microenvironment is critical for tumorigenesis and Cancer progression. The extracellular matrix (ECM) interacts with tumor and stromal cells to promote Cancer cells proliferation, migration, invasion, angiogenesis and immune evasion. Both ECM itself and ECM stiffening-induced mechanical stimuli may activate cell membrane receptors and mechanosensors such as Integrin, Piezo1 and TRPV4, thereby modulating the malignant phenotype of tumor and stromal cells. A better understanding of how ECM stiffness regulates tumor progression will contribute to the development of new therapeutics. The rapidly expanding evidence in this Research Area suggests that the regulators and effectors of ECM stiffness represent potential therapeutic targets for Cancer. This review summarizes recent work on the regulation of ECM stiffness in Cancer, the effects of ECM stiffness on tumor progression, Cancer immunity and drug resistance. We also discuss the potential targets that may be druggable to intervene ECM stiffness and tumor progression. Based on these advances, future efforts can be made to develop more effective and safe drugs to interrupt ECM stiffness-induced oncogenic signaling, Cancer progression and drug resistance.

Keywords

Cancer; Cancer therapy; Drug resistance; ECM stiffness; Extracellular matrix; Mechanotransducer; Piezo.

Figures
Products