The fluid shear stress sensor TRPM7 regulates tumor cell intravasation
Mostra el registre complet Registre parcial de l'ítem
- dc.contributor.author Yankaskas, Christopher L.
- dc.contributor.author Bera, Kaustav
- dc.contributor.author Stoletov, Konstantin
- dc.contributor.author Serra, Selma A.
- dc.contributor.author Carrillo García, Julia, 1993-
- dc.contributor.author Tuntithavornwat, Soontorn
- dc.contributor.author Mistriotis, Panagiotis
- dc.contributor.author Lewis, John D.
- dc.contributor.author Valverde, M. A. (Miguel Ángel), 1963-
- dc.contributor.author Konstantopoulos, Konstantinos
- dc.date.accessioned 2021-08-24T06:51:22Z
- dc.date.available 2021-08-24T06:51:22Z
- dc.date.issued 2021
- dc.description.abstract Tumor cell intravasation preferentially occurs in regions of low fluid shear because high shear is detrimental to tumor cells. Here, we describe a molecular mechanism by which cells avoid high shear during intravasation. The transition from migration to intravasation was modeled using a microfluidic device where cells migrating inside longitudinal tissue-like microchannels encounter an orthogonal channel in which fluid flow induces physiological shear stresses. This approach was complemented with intravital microscopy, patch-clamp, and signal transduction imaging techniques. Fluid shear-induced activation of the transient receptor potential melastatin 7 (TRPM7) channel promotes extracellular calcium influx, which then activates RhoA/myosin-II and calmodulin/IQGAP1/Cdc42 pathways to coordinate reversal of migration direction, thereby avoiding shear stress. Cells displaying higher shear sensitivity due to higher TRPM7 activity levels intravasate less efficiently and establish less invasive metastatic lesions. This study provides a mechanistic interpretation for the role of shear stress and its sensor, TRPM7, in tumor cell intravasation.
- dc.format.mimetype application/pdf
- dc.identifier.citation Yankaskas CL, Bera K, Stoletov K, Serra SA, Carrillo-Garcia J, Tuntithavornwat S, Mistriotis P, Lewis JD, Valverde MA, Konstantopoulos K. The fluid shear stress sensor TRPM7 regulates tumor cell intravasation. Sci Adv. 2021;7(28):eabh3457. DOI: 10.1126/sciadv.abh3457
- dc.identifier.doi http://dx.doi.org/10.1126/sciadv.abh3457
- dc.identifier.issn 2375-2548
- dc.identifier.uri http://hdl.handle.net/10230/48326
- dc.language.iso eng
- dc.publisher American Association for the Advancement of Science (AAAS)
- dc.relation.ispartof Sci Adv. 2021;7(28):eabh3457
- dc.rights © 2021 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 NonCommercial License 4.0 (CC BY-NC).
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri https://creativecommons.org/licenses/by-nc/4.0/
- dc.title The fluid shear stress sensor TRPM7 regulates tumor cell intravasation
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion