PUBLICATION
Vimentin Promotes the Aggressiveness of Triple Negative Breast Cancer Cells Surviving Chemotherapeutic Treatment
- Authors
- Winter, M., Meignan, S., Völkel, P., Angrand, P.O., Chopin, V., Bidan, N., Toillon, R.A., Adriaenssens, E., Lagadec, C., Le Bourhis, X.
- ID
- ZDB-PUB-210703-14
- Date
- 2021
- Source
- Cells 10(6): (Journal)
- Registered Authors
- Völkel, Pamela
- Keywords
- cancer stem cells, chemotherapy resistance, invasion, triple negative breast cancer, vimentin, zebrafish xenografts
- MeSH Terms
-
- Animals
- Cell Line, Tumor
- Cell Movement/physiology
- Cyclophosphamide/pharmacology
- Disease Models, Animal
- Drug Resistance, Neoplasm/physiology*
- Drug Therapy/methods
- Epirubicin/pharmacology
- Epithelial-Mesenchymal Transition
- Female
- Humans
- Neoadjuvant Therapy/methods
- Neoplasm Invasiveness/pathology
- Neoplasm Recurrence, Local
- Paclitaxel/therapeutic use
- Triple Negative Breast Neoplasms/metabolism*
- Triple Negative Breast Neoplasms/pathology
- Vimentin/metabolism
- Vimentin/physiology*
- Zebrafish
- PubMed
- 34203746 Full text @ Cells
Citation
Winter, M., Meignan, S., Völkel, P., Angrand, P.O., Chopin, V., Bidan, N., Toillon, R.A., Adriaenssens, E., Lagadec, C., Le Bourhis, X. (2021) Vimentin Promotes the Aggressiveness of Triple Negative Breast Cancer Cells Surviving Chemotherapeutic Treatment. Cells. 10(6):.
Abstract
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 vimentinhigh 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping