期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 502, 期 1, 页码 137-144出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2018.05.136
关键词
Breast cancer; Tissue factor (TF); Extracellular vesicles; Microvesicles (MVs)
资金
- Brazilian National Council for Scientific and Technological Development (CNPq) [141907/2012-6, 302115/2017-0]
- Science without Borders (CNPq) [211724/2013-0]
- State of Rio de Janeiro Research Foundation (FAPERJ) [E-26/202.528/2016, E-26/203.028/2015, E-26/203.185/2015]
- Worldwide Cancer Research [15-1186]
Extracellular vesicles, such as microvesicles (MVs), were identified as important players in tumor progression and acquisition of an aggressive phenotype. Tissue factor (TF) is a transmembrane protein that initiates the blood coagulation cascade. In tumor cells, TF has been associated with aggressiveness and cancer progression. Previous studies demonstrate that TF is incorporated into MVs secreted by tumor cells; however, it is unknown whether TF is actively involved in the release of MVs. Here, we investigated the influence of TF expression on the release of MVs. TF silencing was achieved through CRISPR/Cas9 approaches in the human breast cancer cell line, MDA-MB-231. TF knockout in MDA-MB-231 cells efficiently reduced TF-dependent signaling and procoagulant activity. Remarkably, silencing of TF caused a significant decrease in the number of MVs released by MDA-MB-231 cells. We also observed an increase in actin-positive membrane projections in TF knockout cells and a reduction in RhoA expression when compared to TF-expressing cells. Treatment of MDA-MB-231 cells with the RhoA-ROCK signaling pathway inhibitor, fasudil, significantly reduced the release of MVs. Taken together, our results suggest a novel and relevant role for TF in tumor biology by playing an active role in the MVs secretion. (C) 2018 Elsevier Inc. All rights reserved.
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