Cell Biology

A ROCK, a Tumor Cell, and a Hard Place

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Science  23 Sep 2005:
Vol. 309, Issue 5743, pp. 1967
DOI: 10.1126/science.309.5743.1967a

Tumors are generally stiffer than surrounding healthy tissue, a characteristic that has been exploited in certain diagnostic procedures such as breast self-examination. Tumor rigidity reflects not only intrinsic properties of the tumor cells but also an increased stiffness of the extracellular matrix (ECM). Whether ECM stiffening plays an active role in tumor cell growth or is an innocent bystander has been unclear.

Paszek et al. investigated this question by monitoring the behavior of human mammary epithelial cells cultured with ECM components that had been cross-linked to polyacrylamide gels of varying stiffness. These experiments revealed that even a small increase in matrix rigidity enhanced epithelial cell growth. Mechanistically, this effect was traced to a mechano-regulatory circuit that links physical cues from the matrix to transmembrane ECM receptors (integrins), to intracellular regulators of cell contractility such as ROCK (Rho-associated protein kinase), and to a key signaling pathway for cell growth, the mitogen-activated protein kinase pathway. These results suggest that factors causing a sustained increase in matrix stiffness—for example, a chronic inflammatory response—may promote malignant transformation. — PAK

Cancer Cell, in press.

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