当前位置： SCI文献检索 > OncoTargets and Therapy期刊下所有文献 > Connexin 43 Modulates the Cellular Resistance to Paclitaxel via Targeting β-Tubulin in Triple-Negative Breast Cancer.

Connexin 43 Modulates the Cellular Resistance to Paclitaxel via Targeting β-Tubulin in Triple-Negative Breast Cancer.

Abstract：

Background:Triple-negative breast cancer has become an intricate part and hotspot in the clinical and experimental research. Connexins, serving as functional proteins in gap junctions, play an important role in tumorigenesis, cell proliferation and metastasis. Methods:We constructed and employed the Connexin 43 (Cx43) overexpression lentiviral vectors and Cx43 siRNA in paclitaxel-treated MDA-MB-231 cells. We performed the experiments of clonal formation and flow cytometry to gauge the effect of paclitaxel on cellular behaviors and immunofluorescence and subsequent quantitative RT-PCR and Western blot to examine the expression of genes and corresponding proteins. Experiments of scrape loading/dye transfer were utilized to explore the gap junctions. The targets of Cx43 were identified via the experiments of co-immunoprecipitation (Co-IP), GST pull-down assays and proximal ligation assay (PLA). Results:The results showed that Cx43 hindered cell proliferation and promoted apoptosis in the paclitaxel-treated MDA-MB-231 cells. Overexpressed Cx43 suppressed the expression of resistance genes such as BRCP, Txr-1, α-tubulin and β-tubulin and promoted the expression of apoptosis gene as TSP-1 and Bcl-2. Cx43 was also positively related to ITGα9 and negatively related to ITGαV and ITGα11. The gap junctions altered magnificently under different expressions of Cx43, which indicated that Cx43 could promote the number of intercellular gap junctions. The immunofluorescent experiment revealed that both of Cx43 and β-tubulin were mainly localized in the cytoplasm. The assays of Co-IP and GST pull-down demonstrated that there existed a direct interaction between Cx43 and β-tubulin. Furthermore, the result of PLA also showed that Cx43 interacts with β-tubulin in MDA-MB-231 cells. Conclusion:Overexpression of Cx43 could modulate the cellular resistance to paclitaxel via targeting β-tubulin in triple-negative breast cancer.

journal_name

Onco Targets Ther

journal_title

OncoTargets and therapy

authors

Fu Y,Sun X,Gu Z,Zhuang Z

doi

10.2147/OTT.S229076

subject

Has Abstract

pub_date

2020-06-10 00:00:00

pages

5323-5335

issn

1178-6930

pii

229076

journal_volume

pub_type

杂志文章

在线工具

Connexin 43 Modulates the Cellular Resistance to Paclitaxel via Targeting β-Tubulin in Triple-Negative Breast Cancer.