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Role of extrinsic physical cues in cancer progression

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초록

The tumor microenvironment (TME) is a complex system composedof many cell types and an extracellular matrix (ECM). Duringtumorigenesis, cancer cells constantly interact with cellularcomponents, biochemical cues, and the ECM in the TME, allof which make the environment favorable for cancer growth. Emerging evidence has revealed the importance of substrateelasticity and biomechanical forces in tumor progression andmetastasis. However, the mechanisms underlying the cell responseto mechanical signals—such as extrinsic mechanicalforces and forces generated within the TME—are still relativelyunknown. Moreover, having a deeper understanding of themechanisms by which cancer cells sense mechanical forcesand transmit signals to the cytoplasm would substantially helpdevelop effective strategies for cancer treatment. This reviewprovides an overview of biomechanical forces in the TME andthe intracellular signaling pathways activated by mechanical cuesas well as highlights the role of mechanotransductive pathwaysthrough mechanosensors that detect the altering biomechanicalforces in the TME.

Abstract

The tumor microenvironment (TME) is a complex system composedof many cell types and an extracellular matrix (ECM). Duringtumorigenesis, cancer cells constantly interact with cellularcomponents, biochemical cues, and the ECM in the TME, allof which make the environment favorable for cancer growth. Emerging evidence has revealed the importance of substrateelasticity and biomechanical forces in tumor progression andmetastasis. However, the mechanisms underlying the cell responseto mechanical signals—such as extrinsic mechanicalforces and forces generated within the TME—are still relativelyunknown. Moreover, having a deeper understanding of themechanisms by which cancer cells sense mechanical forcesand transmit signals to the cytoplasm would substantially helpdevelop effective strategies for cancer treatment. This reviewprovides an overview of biomechanical forces in the TME andthe intracellular signaling pathways activated by mechanical cuesas well as highlights the role of mechanotransductive pathwaysthrough mechanosensors that detect the altering biomechanicalforces in the TME.

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