Matrix stiffness regulates tumor cell intravasation through expression and ESRP1-mediated alternative splicing of MENA.

Autor:	Wang W; Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37235, USA., Taufalele PV; Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37235, USA., Millet M; CHU de Québec-Université Laval Research Center (Oncology Division), Québec, QC G1R 3S3, Canada; CHU de Québec-Université Laval Research Center (Oncology Division), Québec, QC G1R 3S3, Canada., Homsy K; CHU de Québec-Université Laval Research Center (Oncology Division), Québec, QC G1R 3S3, Canada; CHU de Québec-Université Laval Research Center (Oncology Division), Québec, QC G1R 3S3, Canada., Smart K; Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37235, USA., Berestesky ED; Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37235, USA., Schunk CT; Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37235, USA., Rowe MM; Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37235, USA., Bordeleau F; CHU de Québec-Université Laval Research Center (Oncology Division), Québec, QC G1R 3S3, Canada; CHU de Québec-Université Laval Research Center (Oncology Division), Québec, QC G1R 3S3, Canada; Département de biologie moléculaire, de biochimie médicale et de pathologie, Université Laval, Québec, QC G1V 0A6, Canada. Electronic address: francois.bordeleau@fmed.ulaval.ca., Reinhart-King CA; Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37235, USA. Electronic address: cynthia.reinhart-king@vanderbilt.edu.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2023 Apr 25; Vol. 42 (4), pp. 112338. Date of Electronic Publication: 2023 Apr 05.
DOI:	10.1016/j.celrep.2023.112338
Abstrakt:	During intravasation, cancer cells cross the endothelial barrier and enter the circulation. Extracellular matrix stiffening has been correlated with tumor metastatic potential; however, little is known about the effects of matrix stiffness on intravasation. Here, we utilize in vitro systems, a mouse model, specimens from patients with breast cancer, and RNA expression profiles from The Cancer Genome Atlas Program (TCGA) to investigate the molecular mechanism by which matrix stiffening promotes tumor cell intravasation. Our data show that heightened matrix stiffness increases MENA expression, which promotes contractility and intravasation through focal adhesion kinase activity. Further, matrix stiffening decreases epithelial splicing regulatory protein 1 (ESRP1) expression, which triggers alternative splicing of MENA, decreases the expression of MENA 11a , and enhances contractility and intravasation. Altogether, our data indicate that matrix stiffness regulates tumor cell intravasation through enhanced expression and ESRP1-mediated alternative splicing of MENA, providing a mechanism by which matrix stiffness regulates tumor cell intravasation. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu