Thesis - Open Access
Master of Science (MS)
Chemistry and Biochemistry
Séverine Van slambrouck
actin, cancer, Cell-cell adhesion, migration, Non-muscle myosin II
Loss of cell-cell adhesion and migration are prerequisites for the formation of metastases. These events are mediated by changes in the actomyosin cytoskeleton. Nonmuscle myosin II (NMII) belongs to the myosin superfamily of motor proteins which binds to actin and controls actin cross-linking and contraction, however its role and regulation in cell-adhesion and migration remains poorly understood. In this study, we report that associations of α5β1integrin receptors and Ncadherins with NMII isoforms NM-IIA and NMII-B correlate with increased cell-cell adhesion and reduced migratory behavior of the parental Hs578T cells of the Hs578T/Hs578Ts(i)8 triple-negative breast cancer progression model. Using blebbistatin, a pharmacological inhibitor of NMII ATPase activity which decreases non-muscle myosin II contraction, on Hs578T cells induced loss of cell-cell adhesion and increased migration which was comparable to the behavior of the invasive Hs578Ts(i)8 subclone. The blebbistatin-mediated NMII inhibition in Hs578T cells not only stimulated the polymerization of F-actin, but also the formation of highly organized F-actin, myosin The blebbistatin-mediated NMII inhibition in Hs578T cells not only stimulated the polymerization of F-actin, but also the formation of highly organized F-actin, myosin fibers and actin-rich protrusions with more nascent paxillin and talin-1 based focal adhesion complexes, while reducing N-cadherin and α5β1 integrin receptor clustering at cell-cell junctions. These findings provide novel insights into the role of NMII in the regulation of cell-cell adhesion and migration by linking N-cadherin and integrins to the actomyosin cytoskeleton to maintain stable cell-cell adhesion complexes.
Library of Congress Subject Headings
Breast -- Cancer.
Includes bibliographical references (pages 72-77)
Number of Pages
South Dakota State University
In Copyright - Educational Use Permitted
Gunawardana, Shimara, "Role of Non-muscle Myosin II In Hs578T/Hs578Ts(i)8 Triple Negative Breast Cancer Progression" (2018). Electronic Theses and Dissertations. 2460.