Document Type

Thesis - Open Access

Award Date

2018

Degree Name

Master of Science (MS)

Department

Chemistry and Biochemistry

First Advisor

Séverine Van slambrouck

Keywords

actin, cancer, Cell-cell adhesion, migration, Non-muscle myosin II

Abstract

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.
Cancer invasiveness.
Metastasis.
Myosin.
Cell adhesion.

Description

Includes bibliographical references (pages 72-77)

Format

application/pdf

Number of Pages

89

Publisher

South Dakota State University

Rights

In Copyright - Educational Use Permitted
http://rightsstatements.org/vocab/InC-EDU/1.0/

Included in

Chemistry Commons

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