静脉注射
细胞外基质
细胞生物学
选择性拼接
癌症研究
变硬
生物
癌细胞
癌症
遗传学
材料科学
信使核糖核酸
基因
复合材料
作者
Wenjun Wang,Paul V. Taufalele,Martial Millet,Kevin Homsy,Kyra Smart,Emily D Berestesky,Curtis Schunk,Matthew M. Rowe,François Bordeleau,Cynthia A. Reinhart‐King
出处
期刊:Cell Reports
[Elsevier]
日期:2023-04-01
卷期号:42 (4): 112338-112338
被引量:7
标识
DOI:10.1016/j.celrep.2023.112338
摘要
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.
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