Direct measurement of vertical forces shows correlation between mechanical activity and proteolytic ability of invadopodia
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Mechanobiology plays a prominent role in cancer invasion and metastasis. The ability of a cancer to degrade extracellular matrix (ECM) is likely connected to its invasiveness. Many cancer cells form invadopodia—micrometer-sized cellular protrusions that promote invasion through matrix degradation (proteolysis). Although it has been hypothesized that invadopodia exert mechanical force that is implicated in cancer invasion, direct measurements remain elusive. Here, we use a recently developed interferometric force imaging technique that provides piconewton resolution to quantify invadopodial forces in cells of head and neck squamous carcinoma and to monitor their temporal dynamics. We compare the force exerted by individual protrusions to their ability to degrade ECM and investigate the mechanical effects of inhibiting invadopodia through overexpression of microRNA-375. By connecting the biophysical and biochemical characteristics of invadopodia, our study provides a new perspective on cancer invasion that, in the future, may help to identify biomechanical targets for cancer therapy.
Dalaka , E , Kronenberg , N M , Liehm , P , Segall , J E , Prystowsky , M B & Gather , M C 2020 , ' Direct measurement of vertical forces shows correlation between mechanical activity and proteolytic ability of invadopodia ' , Science Advances , vol. 6 , no. 11 , eaax6912 . https://doi.org/10.1126/sciadv.aax6912
Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S.Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY),
DescriptionFunding: European Research Council under the European Union’s Horizon 2020 Framework Programme (ERC StG ABLASE, 640012); BBSRC (BB/P027148/1); EPSRC Programme Grant (EP/P030017/1); EPSRC Doctoral Training Partnership (EP/N509759/1, EP/L505079/1).
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