The tropomyosin 3.1/3.2 inhibitor ATM-3507 alters B-cell actin dynamics and impairs the growth and motility of diffuse large B-cell lymphoma cell lines
Abhishek Bedi, Kate Choi, Alyssa Iskierski, Michael R. Gold
TL;DR
A drug called ATM-3507 disrupts actin structures in B cells and reduces the growth and movement of diffuse large B-cell lymphoma cells.
Contribution
This study identifies Tpm3.1/3.2 as a novel therapeutic target in diffuse large B-cell lymphoma.
Findings
ATM-3507 inhibits B-cell receptor-induced actin ring formation and actomyosin arcs.
ATM-3507 treatment blocks DLBCL cell growth and causes G2/M phase accumulation.
ATM-3507 significantly reduces chemotaxis and integrin-dependent motility of DLBCL cells.
Abstract
By stabilizing actin filaments and recruiting non-muscle myosin II, the closely related tropomyosin (Tpm) isoforms Tpm3.1 and Tpm3.2 support actin-dependent processes including membrane dynamics, cell migration, and cytokinesis. Actin dynamics are essential for B cell function, but the roles of Tpm3.1 and 3.2 (collectively termed Tpm3.1/3.2) in B cells have not been explored. Moreover, new treatments are needed to limit the growth and dissemination of diffuse large B-cell lymphoma (DLBCL), the most prevalent B-cell malignancy. To test whether Tpm3.1/3.2 is essential for B-cell actin dynamics and could be a target for treating DLBCL, we employed ATM-3507, a compound that selectively interferes with Tpm3.1/3.2 function. We show that ATM-3507 treatment inhibited B-cell receptor-induced formation of the peripheral ring of branched actin that drives cell spreading and also prevented the…
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Taxonomy
TopicsCardiomyopathy and Myosin Studies · Cellular Mechanics and Interactions · Cell Adhesion Molecules Research