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Tumor Stiffness Is Unrelated to Myosin Light Chain Phosphorylation in Cancer Cells

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posted on 12.04.2016 by Hui-Jun Yu, Leonid A Serebryannyy, Madeline Fry, Madelyne Greene, Olga Chernaya, Wen-Yang Hu, Teng-Leong Chew, Nadim Mahmud, Shrihari S Kadkol, Sarah Glover, Gail Prins, Zuzana Strakova, Primal de Lanerolle
Many tumors are stiffer than their surrounding tissue. This increase in stiffness has been attributed, in part, to a Rho-dependent elevation of myosin II light chain phosphorylation. To characterize this mechanism further, we studied myosin light chain kinase (MLCK), the main enzyme that phosphorylates myosin II light chains. We anticipated that increases in MLCK expression and activity would contribute to the increased stiffness of cancer cells. However, we find that MLCK mRNA and protein levels are substantially less in cancer cells and tissues than in normal cells. Consistent with this observation, cancer cells contract 3D collagen matrices much more slowly than normal cells. Interestingly, inhibiting MLCK or Rho kinase did not affect the 3D gel contractions while blebbistatin partially and cytochalasin D maximally inhibited contractions. Live cell imaging of cells in collagen gels showed that cytochalasin D inhibited filopodia-like projections that formed between cells while a MLCK inhibitor had no effect on these projections. These data suggest that myosin II phosphorylation is dispensable in regulating the mechanical properties of tumors.

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Funding

Supported in part by grants from Northwestern University Physical Sciences Oncology Center (CA143869) sub-award to PdeL, from National Institutes of Health to SG (CA113975), GP (ES018758, ES02207 and CA172220) and ZS (ARRA HD044713), the Leukemia and Lymphoma Society (White Plains, New York, United States of America), The American Gastroenterological Association and UIC Gastrointestinal and Liver Disease fund to SG, an Areas of Excellence Award from the Office of the Vice Chancellor for Research, UIC to NM and an American Heart Association fellowship (13PRE17050060) to LAS. The authors certify that they have no competing financial interests. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Publisher Statement

Copyright: © 2013 Yu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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Public Library of Science

Language

en_US

issn

1932-6203

Issue date

01/01/2013

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