Wnt/β-Catenin Inhibition Disrupts Carboplatin Resistance in Isogenic Models of Triple-Negative Breast Cancer.
WNT pathway
cancer stem cells
patient-derived xenograft models
platinum-resistance
triple negative breast cancer
Journal
Frontiers in oncology
ISSN: 2234-943X
Titre abrégé: Front Oncol
Pays: Switzerland
ID NLM: 101568867
Informations de publication
Date de publication:
2021
2021
Historique:
received:
05
05
2021
accepted:
28
06
2021
entrez:
9
8
2021
pubmed:
10
8
2021
medline:
10
8
2021
Statut:
epublish
Résumé
Triple-Negative Breast Cancer (TNBC) is the most aggressive breast cancer subtype, characterized by limited treatment options and higher relapse rates than hormone-receptor-positive breast cancers. Chemotherapy remains the mainstay treatment for TNBC, and platinum salts have been explored as a therapeutic alternative in neo-adjuvant and metastatic settings. However, primary and acquired resistance to chemotherapy in general and platinum-based regimens specifically strongly hampers TNBC management. In this study, we used carboplatin-resistant in vivo patient-derived xenograft and isogenic TNBC cell-line models and detected enhanced Wnt/β-catenin activity correlating with an induced expression of stem cell markers in both resistant models. In accordance, the activation of canonical Wnt signaling in parental TNBC cell lines increases stem cell markers' expression, formation of tumorspheres and promotes carboplatin resistance. Finally, we prove that Wnt signaling inhibition resensitizes resistant models to carboplatin both in vitro and in vivo, suggesting the synergistic use of Wnt inhibitors and carboplatin as a therapeutic option in TNBC. Here we provide evidence for a prominent role of Wnt signaling in mediating resistance to carboplatin, and we establish that combinatorial targeting of Wnt signaling overcomes carboplatin resistance enhancing chemotherapeutic drug efficacy.
Identifiants
pubmed: 34367990
doi: 10.3389/fonc.2021.705384
pmc: PMC8340846
doi:
Types de publication
Journal Article
Langues
eng
Pagination
705384Informations de copyright
Copyright © 2021 Abreu de Oliveira, Moens, El Laithy, van der Veer, Athanasouli, Cortesi, Baietti, Koh, Ventura, Amant, Annibali and Lluis.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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