Vimentin Promotes the Aggressiveness of Triple Negative Breast Cancer Cells Surviving Chemotherapeutic Treatment

Cells

Robert-Alain Toillon¹  Xuefen Le Bourhis¹  Marie Winter¹  Pierre-Olivier Angrand¹  Valérie Chopin¹  Pamela Völkel¹  Samuel Meignan¹  Nadège Bidan¹  Chann Lagadec¹  Eric Adriaenssens¹ 

[1] UMR9020—U1277-CANTHER—Cancer Heterogeneity, Plasticity and Resistance to Therapies, University of Lille, CNRS, Inserm, CHU Lille, F-59000 Lille, France;

关键词: triple negative breast cancer;    chemotherapy resistance;    invasion;    cancer stem cells;    vimentin;    zebrafish xenografts;   

DOI  :  10.3390/cells10061504

来源: DOAJ

【 摘 要 】

Tremendous data have been accumulated in the effort to understand chemoresistance of triple negative breast cancer (TNBC). However, modifications in cancer cells surviving combined and sequential treatment still remain poorly described. In order to mimic clinical neoadjuvant treatment, we first treated MDA-MB-231 and SUM159-PT TNBC cell lines with epirubicin and cyclophosphamide for 2 days, and then with paclitaxel for another 2 days. After 4 days of recovery, persistent cells surviving the treatment were characterized at both cellular and molecular level. Persistent cells exhibited increased growth and were more invasive in vitro and in zebrafish model. Persistent cells were enriched for vimentin^high sub-population, vimentin knockdown using siRNA approach decreased the invasive and sphere forming capacities as well as Akt phosphorylation in persistent cells, indicating that vimentin is involved in chemotherapeutic treatment-induced enhancement of TNBC aggressiveness. Interestingly, ectopic vimentin overexpression in native cells increased cell invasion and sphere formation as well as Akt phosphorylation. Furthermore, vimentin overexpression alone rendered the native cells resistant to the drugs, while vimentin knockdown rendered them more sensitive to the drugs. Together, our data suggest that vimentin could be considered as a new targetable player in the ever-elusive status of drug resistance and recurrence of TNBC.

【 授权许可】

Unknown