Quercetin Impairs HuR-Driven Progression and Migration of Triple Negative Breast Cancer (TNBC) Cells

Abstract

In the present study, we have explored the prognostic value of HuR gene as well as protein in breast cancers. Furthermore, we have also investigated the HuR therapeutic relevance in TNBCs, which is an aggressive breast cancer subtype. Using an online meta-analysis tool, we found that HuR protein overexpression positively correlates with reduced overall survival of TNBC patients (p = 0.028). Furthermore, we demonstrated that the TNBC breast cancer cell lines i.e., MDA-MB-231 and MDA-MB-468 are good model systems to study HuR protein, as they both exhibit a significant amount of cytoplasmic HuR (active form). Quercetin treatment significantly inhibited the cytoplasmic HuR in both TNBC cell lines. By using specific HuR siRNA, we established that quercetin-mediated inhibition of adhesion and migration of TNBC cells is dependent on HuR. Upon analyzing adhesion proteins i.e., β-catenin and CD44, we found that quercetin mediated effect on TNBC adhesion and migration was through the HuR-β-catenin axis and CD44, independently. Overall, the present results demonstrate that elevated HuR levels are associated with TNBC progression and relapse, and the ability of quercetin to inhibit cytoplasmic HuR protein provides a rationale for using it as an anticancer agent for the treatment of aggressive TNBCs.

Supplemental data for this article is available online at at 10.1080/01635581.2021.1952628.

Acknowledgments

The authors also like to thank the ‘Central Flow-Cytometry Facility of Dr. BRA IRCH, AIIMS ‘ for CD44 analysis.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was in part supported by AIIMS Intramural grants (No. A-515) to Chandra Prakash Prasad. The funders had no role in study design, data collection, data analysis, decision to publish, or preparation of the manuscript