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Biomechanical regulation of cell orientation and fate

Abstract

Biomechanical regulation of tumor phenotypes have been noted for several decades, yet the function of mechanics in the co-evolution of the tumor epithelium and altered cancer extracellular matrix has not been appreciated until fairly recently. In this review, we examine the dynamic interaction between the developing epithelia and the extracellular matrix, and discuss how similar interactions are exploited by the genetically modified epithelium during tumor progression. We emphasize the process of mechanoreciprocity, which is a phenomenon observed during epithelial transformation, in which tension generated within the extracellular microenvironment induce and cooperate with opposing reactive forces within transformed epithelium to drive tumor progression and metastasis. We highlight the importance of matrix remodeling, and present a new, emerging paradigm that underscores the importance of tissue morphology as a key regulator of epithelial cell invasion and metastasis.

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Acknowledgements

We apologize to the authors whose work is not cited because of space limitations. This work was supported by NIH Grant 7R01CA078731-07, DOD Breast Cancer Research Era of Hope Grant W81XWH-05-1-330 (BC044791), CIRM Grant RS1-00449 and DOE Grant A107165 to VMW, NIH NCI Training Grant 5T32CA108462-04 to JL and DOD Breast Cancer Research Era of Hope Grant BC06262 to JM.

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Lopez, J., Mouw, J. & Weaver, V. Biomechanical regulation of cell orientation and fate. Oncogene 27, 6981–6993 (2008). https://doi.org/10.1038/onc.2008.348

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  • DOI: https://doi.org/10.1038/onc.2008.348

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