期刊
CURRENT STEM CELL REPORTS
卷 7, 期 1, 页码 39-47出版社
SPRINGER HEIDELBERG
DOI: 10.1007/s40778-020-00182-2
关键词
Cancer stem cell; Tumor microenvironment; Mechano-signaling; Extracellular matrix; Signaling integration
资金
- CDMRP BCRP Era of Hope Award [BC141351, BC181737]
- NIH [R01EB024989, U54HG008100]
- Conrad N. Hilton Foundation
- City of Hope Center for Cancer and Aging
Cancer stem cells (CSCs) play a central role in tumor progression and are regulated by signals from the tumor microenvironment. The mechanical properties and extracellular matrix composition of the microenvironment influence CSC growth and survival through integrins and other cell surface receptors. Understanding the signaling that maintains cells in CSC states may guide future therapeutic interventions.
Purpose of Review Cancer stem cells (CSCs) are increasingly understood to play a central role in tumor progression. Growing evidence implicates tumor microenvironments as a source of signals that regulate or even impose CSC states on tumor cells. This review explores points of integration for microenvironment-derived signals that are thought to regulate CSCs in carcinomas. Recent Findings CSC states are directly regulated by the mechanical properties and extracellular matrix (ECM) composition of tumor microenvironments that promote CSC growth and survival, which may explain some modes of therapeutic resistance. CSCs sense mechanical forces and ECM composition through integrins and other cell surface receptors, which then activate a number of intracellular signaling pathways. The relevant signaling events are dynamic and context-dependent. Summary CSCs are thought to drive cancer metastases and therapeutic resistance. Cells that are in CSC states and more differentiated states appear to be reversible and conditional upon the components of the tumor microenvironment. Signals imposed by tumor microenvironment are of a combinatorial nature, ultimately representing the integration of multiple physical and chemical signals. Comprehensive understanding of the tumor microenvironment-imposed signaling that maintains cells in CSC states may guide future therapeutic interventions.
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