Abstract
Triple-negative breast cancer (TNBC) is a highly metastatic breast cancer subtype, and the primary systemic treatment strategy involves conventional chemotherapy. DC-STAMP domain containing 1-antisense 1 (DCST1-AS1) is a long non-coding RNA that promotes TNBC migration and invasion. Studying the role of DCST1-AS1 in promoting epithelial–mesenchymal transition (EMT) and chemoresistance will provide a new strategy for TNBC therapy. In the present study, we found that DCST1-AS1 regulates the expression or secretion of EMT-related proteins E-cadherin, snail family zinc finger 1 (SNAI1), vimentin, matrix metallopeptidase 2 (MMP2), and matrix metallopeptidase 9 (MMP9). Interference with DCST1-AS1 impaired TGF-β-induced TNBC cell invasion and migration. DCST1-AS1 directly binds to ANXA1 in BT-549 cells and affects the expression of ANXA1. DCST1-AS1 enhances TGF-β/Smad signaling in BT-549 cells through ANXA1 to promote EMT. The combination of DCST1-AS1 and ANXA1 also contributes to enhancement of the resistance of BT-549 cells to doxorubicin and paclitaxel. In conclusion, DCST1-AS1 promotes TGF-β-induced EMT and enhances chemoresistance in TNBC cells through ANXA1, and therefore represents a potentially promising target for metastatic breast cancer therapy.
Highlights
Breast cancer is a highly heterogeneous disease
These results indicate that DCST1-AS1 affects TGF-β-induced vimentin and E-cadherin expression in BT-549 and MDA-MB-231 cells
We found that Annexin A1 (ANXA1) is expressed significantly higher in the triple-negative breast cancer (TNBC) subtype than in the luminal and HER2+ types (Figure 4A)
Summary
The classification of breast cancer is generally based on histological subtypes associated with unique clinical manifestations or molecular features identified by gene expression analysis. The most popular classification is the one based on molecular subtypes determined by gene expression profiling proposed by the expert panel at the St Gallen International Breast Cancer Conference in 2013 [1] and includes luminal A, luminal B, human epidermal growth factor receptor 2-positive (HER2+) overexpressing, and basal-like (BL) subtypes. 77% of BL tumors exhibit loss of expression of the estrogen receptor, progesterone receptor, and HER2, and are referred to as triple-negative breast cancer (TNBC) [4]. Due to the lack of expression of hormone receptors and the absence of HER2 protein overexpression, there is currently no targeted therapy for this breast cancer subtype, and chemotherapy remains the standard treatment for patients with triple-negative disease
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
