Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China.
School of Medicine, Zhejiang University, Hangzhou, 310003, China.
Signal Transduct Target Ther. 2021 Apr 23;6(1):153. doi: 10.1038/s41392-021-00544-0.
The extracellular matrix (ECM) is one of the major components of tumors that plays multiple crucial roles, including mechanical support, modulation of the microenvironment, and a source of signaling molecules. The quantity and cross-linking status of ECM components are major factors determining tissue stiffness. During tumorigenesis, the interplay between cancer cells and the tumor microenvironment (TME) often results in the stiffness of the ECM, leading to aberrant mechanotransduction and further malignant transformation. Therefore, a comprehensive understanding of ECM dysregulation in the TME would contribute to the discovery of promising therapeutic targets for cancer treatment. Herein, we summarized the knowledge concerning the following: (1) major ECM constituents and their functions in both normal and malignant conditions; (2) the interplay between cancer cells and the ECM in the TME; (3) key receptors for mechanotransduction and their alteration during carcinogenesis; and (4) the current therapeutic strategies targeting aberrant ECM for cancer treatment.
细胞外基质(ECM)是肿瘤的主要成分之一,它在多个关键过程中发挥着作用,包括提供机械支撑、调节微环境以及作为信号分子的来源。ECM 成分的数量和交联状态是决定组织硬度的主要因素。在肿瘤发生过程中,癌细胞与肿瘤微环境(TME)之间的相互作用通常会导致 ECM 的硬度发生改变,从而导致异常的力学转导,并进一步导致恶性转化。因此,全面了解 TME 中 ECM 的失调将有助于发现有希望的癌症治疗的治疗靶点。本文总结了以下几个方面的知识:(1)正常和恶性条件下 ECM 的主要成分及其功能;(2)TME 中癌细胞与 ECM 的相互作用;(3)力学转导的关键受体及其在癌变过程中的改变;以及(4)针对癌症治疗中异常 ECM 的当前治疗策略。