Feeling stress: the mechanics of cancer progression and aggression.
- 1University of California, San Francisco, United States
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.
Keywords: Cancer Progression, Cell contractility, Mechanical stresses, tissue tension, Solid stress, ECM stiffness, therapeutic targets
Received: 30 Nov 2017;
Accepted: 06 Feb 2018.
Edited by:Mark A. LaBarge, Irell & Manella Graduate School of Biological Sciences, City of Hope, United States
Reviewed by:MASARU MIYANO, Lawrence Berkeley National Laboratory (LBNL), United States
James Lorens, University of Bergen, Norway
Fanny A. Pelissier Vatter, Weill Cornell Medical College, Cornell University, United States
Copyright: © 2018 Northcott, Dean, Mouw and Weaver. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Dr. Valerie M. Weaver, University of California, San Francisco, San Francisco, United States, firstname.lastname@example.org