Feeling Stress: The Mechanics of Cancer Progression and Aggression

Frontiers in Cell and Developmental Biology

Ivory S. Dean³  Janna K. Mouw³  Josette M. Northcott³  Valerie M. Weaver⁵ 

[1] Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, United States;Department of Radiation Oncology, University of California, San Francisco, San Francisco, CA, United States;Department of Surgery, Center for Bioengineering and Tissue Regeneration, University of California, San Francisco, San Francisco, CA, United States;Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA, United States;UCSF Helen Diller Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, United States;

关键词: cancer progression;    cell contractility;    mechanical stresses;    tissue tension;    solid stress;    ECM stiffness;   

DOI  :  10.3389/fcell.2018.00017

来源: DOAJ

【 摘 要 】

The tumor microenvironment is a dynamic landscape in which the physical and mechanical properties evolve dramatically throughout cancer progression. These changes are driven by enhanced tumor cell contractility and expansion of the growing tumor mass, as well as through alterations to the material properties of the surrounding extracellular matrix (ECM). Consequently, tumor cells are exposed to a number of different mechanical inputs including cell–cell and cell-ECM tension, compression stress, interstitial fluid pressure and shear stress. Oncogenes engage signaling pathways that are activated in response to mechanical stress, thereby reworking the cell's intrinsic response to exogenous mechanical stimuli, enhancing intracellular tension via elevated actomyosin contraction, and influencing ECM stiffness and tissue morphology. In addition to altering their intracellular tension and remodeling the microenvironment, cells actively respond to these mechanical perturbations phenotypically through modification of gene expression. Herein, we present a description of the physical changes that promote tumor progression and aggression, discuss their interrelationship and highlight emerging therapeutic strategies to alleviate the mechanical stresses driving cancer to malignancy.

【 授权许可】

Unknown