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

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 trea...

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Autores principales: Winter, Marie, Meignan, Samuel, Völkel, Pamela, Angrand, Pierre-Olivier, Chopin, Valérie, Bidan, Nadège, Toillon, Robert-Alain, Adriaenssens, Eric, Lagadec, Chann, Le Bourhis, Xuefen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232646/
https://www.ncbi.nlm.nih.gov/pubmed/34203746
http://dx.doi.org/10.3390/cells10061504
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author Winter, Marie
Meignan, Samuel
Völkel, Pamela
Angrand, Pierre-Olivier
Chopin, Valérie
Bidan, Nadège
Toillon, Robert-Alain
Adriaenssens, Eric
Lagadec, Chann
Le Bourhis, Xuefen
author_facet Winter, Marie
Meignan, Samuel
Völkel, Pamela
Angrand, Pierre-Olivier
Chopin, Valérie
Bidan, Nadège
Toillon, Robert-Alain
Adriaenssens, Eric
Lagadec, Chann
Le Bourhis, Xuefen
author_sort Winter, Marie
collection PubMed
description 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.
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spelling pubmed-82326462021-06-26 Vimentin Promotes the Aggressiveness of Triple Negative Breast Cancer Cells Surviving Chemotherapeutic Treatment Winter, Marie Meignan, Samuel Völkel, Pamela Angrand, Pierre-Olivier Chopin, Valérie Bidan, Nadège Toillon, Robert-Alain Adriaenssens, Eric Lagadec, Chann Le Bourhis, Xuefen Cells Article 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. MDPI 2021-06-15 /pmc/articles/PMC8232646/ /pubmed/34203746 http://dx.doi.org/10.3390/cells10061504 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Winter, Marie
Meignan, Samuel
Völkel, Pamela
Angrand, Pierre-Olivier
Chopin, Valérie
Bidan, Nadège
Toillon, Robert-Alain
Adriaenssens, Eric
Lagadec, Chann
Le Bourhis, Xuefen
Vimentin Promotes the Aggressiveness of Triple Negative Breast Cancer Cells Surviving Chemotherapeutic Treatment
title Vimentin Promotes the Aggressiveness of Triple Negative Breast Cancer Cells Surviving Chemotherapeutic Treatment
title_full Vimentin Promotes the Aggressiveness of Triple Negative Breast Cancer Cells Surviving Chemotherapeutic Treatment
title_fullStr Vimentin Promotes the Aggressiveness of Triple Negative Breast Cancer Cells Surviving Chemotherapeutic Treatment
title_full_unstemmed Vimentin Promotes the Aggressiveness of Triple Negative Breast Cancer Cells Surviving Chemotherapeutic Treatment
title_short Vimentin Promotes the Aggressiveness of Triple Negative Breast Cancer Cells Surviving Chemotherapeutic Treatment
title_sort vimentin promotes the aggressiveness of triple negative breast cancer cells surviving chemotherapeutic treatment
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232646/
https://www.ncbi.nlm.nih.gov/pubmed/34203746
http://dx.doi.org/10.3390/cells10061504
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