Matrix stiffness regulates tumor cell intravasation through expression and ESRP1-mediated alternative splicing of MENA
Summary: 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...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-04-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723003492 |
| _version_ | 1797850910942035968 |
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| author | Wenjun Wang Paul V. Taufalele Martial Millet Kevin Homsy Kyra Smart Emily D. Berestesky Curtis T. Schunk Matthew M. Rowe Francois Bordeleau Cynthia A. Reinhart-King |
| author_facet | Wenjun Wang Paul V. Taufalele Martial Millet Kevin Homsy Kyra Smart Emily D. Berestesky Curtis T. Schunk Matthew M. Rowe Francois Bordeleau Cynthia A. Reinhart-King |
| author_sort | Wenjun Wang |
| collection | DOAJ |
| description | Summary: 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 MENA11a, 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. |
| first_indexed | 2024-04-09T19:09:16Z |
| format | Article |
| id | doaj.art-7fdc709fb6454d83b7c97e3b8661d0fc |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-09T19:09:16Z |
| publishDate | 2023-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-7fdc709fb6454d83b7c97e3b8661d0fc2023-04-07T06:50:10ZengElsevierCell Reports2211-12472023-04-01424112338Matrix stiffness regulates tumor cell intravasation through expression and ESRP1-mediated alternative splicing of MENAWenjun Wang0Paul V. Taufalele1Martial Millet2Kevin Homsy3Kyra Smart4Emily D. Berestesky5Curtis T. Schunk6Matthew M. Rowe7Francois Bordeleau8Cynthia A. Reinhart-King9Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37235, USADepartment of Biomedical Engineering, Vanderbilt University, Nashville, TN 37235, USACHU 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, CanadaCHU 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, CanadaDepartment of Biomedical Engineering, Vanderbilt University, Nashville, TN 37235, USADepartment of Biomedical Engineering, Vanderbilt University, Nashville, TN 37235, USADepartment of Biomedical Engineering, Vanderbilt University, Nashville, TN 37235, USADepartment of Biomedical Engineering, Vanderbilt University, Nashville, TN 37235, USACHU 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; Corresponding authorDepartment of Biomedical Engineering, Vanderbilt University, Nashville, TN 37235, USA; Corresponding authorSummary: 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 MENA11a, 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.http://www.sciencedirect.com/science/article/pii/S2211124723003492CP: Cancer |
| spellingShingle | Wenjun Wang Paul V. Taufalele Martial Millet Kevin Homsy Kyra Smart Emily D. Berestesky Curtis T. Schunk Matthew M. Rowe Francois Bordeleau Cynthia A. Reinhart-King Matrix stiffness regulates tumor cell intravasation through expression and ESRP1-mediated alternative splicing of MENA Cell Reports CP: Cancer |
| title | Matrix stiffness regulates tumor cell intravasation through expression and ESRP1-mediated alternative splicing of MENA |
| title_full | Matrix stiffness regulates tumor cell intravasation through expression and ESRP1-mediated alternative splicing of MENA |
| title_fullStr | Matrix stiffness regulates tumor cell intravasation through expression and ESRP1-mediated alternative splicing of MENA |
| title_full_unstemmed | Matrix stiffness regulates tumor cell intravasation through expression and ESRP1-mediated alternative splicing of MENA |
| title_short | Matrix stiffness regulates tumor cell intravasation through expression and ESRP1-mediated alternative splicing of MENA |
| title_sort | matrix stiffness regulates tumor cell intravasation through expression and esrp1 mediated alternative splicing of mena |
| topic | CP: Cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723003492 |
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