@article {311, title = {Actomyosin-mediated cellular tension drives increased tissue stiffness and β-catenin activation to induce epidermal hyperplasia and tumor growth.}, journal = {Cancer Cell}, volume = {19}, year = {2011}, month = {2011 Jun 14}, pages = {776-91}, abstract = {

Tumors and associated stroma manifest mechanical properties that promote cancer. Mechanosensation of tissue stiffness activates the Rho/ROCK pathway to increase actomyosin-mediated cellular tension to re-establish force equilibrium. To determine how actomyosin tension affects tissue homeostasis and tumor development, we expressed conditionally active ROCK2 in mouse skin. ROCK activation elevated tissue stiffness via increased collagen. β-catenin, a key element of mechanotranscription pathways, was stabilized by ROCK activation leading to nuclear accumulation, transcriptional activation, and consequent hyperproliferation and skin thickening. Inhibiting actomyosin contractility by blocking LIMK or myosin ATPase attenuated these responses, as did FAK inhibition. Tumor number, growth, and progression were increased by ROCK activation, while ROCK blockade was inhibitory, implicating actomyosin-mediated cellular tension and consequent collagen deposition as significant tumor promoters.

}, keywords = {Actomyosin, Animals, beta Catenin, Biomechanical Phenomena, Cell Proliferation, Cells, Cultured, Epidermis, Humans, Hyperplasia, Mice, Papilloma, rho-Associated Kinases, Signal Transduction, Skin Neoplasms}, issn = {1878-3686}, doi = {10.1016/j.ccr.2011.05.008}, author = {Samuel, Michael S and Lopez, Jose I and McGhee, Ewan J and Croft, Daniel R and Strachan, David and Timpson, Paul and Munro, June and Schr{\"o}der, Ewald and Zhou, Jing and Brunton, Valerie G and Barker, Nick and Clevers, Hans and Sansom, Owen J and Anderson, Kurt I and Weaver, Valerie M and Olson, Michael F} } @article {391, title = {Mechanics, malignancy, and metastasis: the force journey of a tumor cell.}, journal = {Cancer Metastasis Rev}, volume = {28}, year = {2009}, month = {2009 Jun}, pages = {113-27}, abstract = {

A cell undergoes many genetic and epigenetic changes as it transitions to malignancy. Malignant transformation is also accompanied by a progressive loss of tissue homeostasis and perturbations in tissue architecture that ultimately culminates in tumor cell invasion into the parenchyma and metastasis to distant organ sites. Increasingly, cancer biologists have begun to recognize that a critical component of this transformation journey involves marked alterations in the mechanical phenotype of the cell and its surrounding microenvironment. These mechanical differences include modifications in cell and tissue structure, adaptive force-induced changes in the environment, altered processing of micromechanical cues encoded in the extracellular matrix (ECM), and cell-directed remodeling of the extracellular stroma. Here, we review critical steps in this \"force journey,\" including mechanical contributions to tissue dysplasia, invasion of the ECM, and metastasis. We discuss the biophysical basis of this force journey and present recent advances in the measurement of cellular mechanical properties in vitro and in vivo. We end by describing examples of molecular mechanisms through which tumor cells sense, process and respond to mechanical forces in their environment. While our understanding of the mechanical components of tumor growth, survival and motility remains in its infancy, considerable work has already yielded valuable insight into the molecular basis of force-dependent tumor pathophysiology, which offers new directions in cancer chemotherapeutics.

}, keywords = {Animals, Biophysics, Cell Transformation, Neoplastic, Epigenesis, Genetic, Extracellular Matrix, Focal Adhesion Protein-Tyrosine Kinases, Humans, Lasers, Microscopy, Atomic Force, Models, Biological, Neoplasm Invasiveness, Neoplasm Metastasis, Neoplasms, rho-Associated Kinases, Stress, Mechanical}, issn = {1573-7233}, doi = {10.1007/s10555-008-9173-4}, author = {Kumar, Sanjay and Weaver, Valerie M} }