Titre :

Colon cancer cells escape 5FU chemotherapy-induced cell death by entering stemness and quiescence associated with the c-Yes/YAP axis

Auteur(s) :

Touil, Yasmine [Auteur]
Igoudjil, Wassila [Auteur]
Corvaisier, Matthieu [Auteur]
Dessein, Anne-Frédérique [Auteur]
Vandomme, Jerome [Auteur]
Monte, Didier [Auteur]
Stechly, Laurence [Auteur]
Skrypek, Nicolas [Auteur]
Langlois, Carole [Auteur]
Grard, Georges [Auteur]
Millet, Guillaume [Auteur]
Leteurtre, Emmanuelle [Auteur]
Dumont, Patrick [Auteur]
Truant, Stéphanie [Auteur]
Pruvot, Francois-Rene [Auteur]
Hebbar, Mohamed [Auteur]
Fan, Fan [Auteur]
Ellis, Lee M. [Auteur]
Formstecher, Pierre [Auteur]
VAN SEUNINGEN, ISABELLE [Auteur]
Gespach, Christian [Auteur]
Polakowska, Renata [Auteur]
Huet, Guillemette [Auteur]

Titre de la revue :

Clinical Cancer Research. An Official Journal of the American Association for Cancer Research

Nom court de la revue :

Clin. Cancer Res.

Numéro :

20

Pagination :

837-846

Date de publication :

2014-02-15

ISSN :

1078-0432

Mot(s)-clé(s) en anglais :

Gene Expression
Cell Proliferation
Humans
Kaplan-Meier Estimate
Proportional Hazards Models
Drug Resistance, Neoplasm
Neoplastic Stem Cells
Liver Neoplasms
Biomarkers, Tumor
Nuclear Proteins
Protein Transport
HT29 Cells
Disease-Free Survival
Cell Cycle Checkpoints
Neoplasm Micrometastasis
Proto-Oncogene Proteins c-yes
Checkpoint Kinase 2
Antimetabolites, Antineoplastic
Neoadjuvant Therapy
Transcription Factors
Chemotherapy, Adjuvant
Cell Nucleus
Colonic Neoplasms
Fluorouracil

Discipline(s) HAL :

Chimie/Chimie théorique et/ou physique

Résumé en anglais : [en]

PURPOSE: Metastasis and drug resistance are the major limitations in the survival and management of patients with cancer. This study aimed to identify the mechanisms underlying HT29 colon cancer cell chemoresistance acquired ...
Lire la suite >PURPOSE: Metastasis and drug resistance are the major limitations in the survival and management of patients with cancer. This study aimed to identify the mechanisms underlying HT29 colon cancer cell chemoresistance acquired after sequential exposure to 5-fluorouracil (5FU), a classical anticancer drug for treatment of epithelial solid tumors. We examined its clinical relevance in a cohort of patients with colon cancer with liver metastases after 5FU-based neoadjuvant chemotherapy and surgery. RESULTS: We show that a clonal 5F31 cell population, resistant to 1 μmol/L 5FU, express a typical cancer stem cell-like phenotype and enter into a reversible quiescent G0 state upon reexposure to higher 5FU concentrations. These quiescent cells overexpressed the tyrosine kinase c-Yes that became activated and membrane-associated upon 5FU exposure. This enhanced signaling pathway induced the dissociation of the Yes/YAP (Yes-associated protein) molecular complex and depleted nuclear YAP levels. Consistently, YES1 silencing decreased nuclear YAP accumulation and induced cellular quiescence in 5F31 cells cultured in 5FU-free medium. Importantly, YES1 and YAP transcript levels were higher in liver metastases of patients with colon cancer after 5FU-based neoadjuvant chemotherapy. Moreover, the YES1 and YAP transcript levels positively correlated with colon cancer relapse and shorter patient survival (P < 0.05 and P < 0.025, respectively). CONCLUSIONS: We identified c-Yes and YAP as potential molecular targets to eradicate quiescent cancer cells and dormant micrometastases during 5FU chemotherapy and resistance and as predictive survival markers for colon cancer.Lire moins >

Langue :

Anglais

Établissement(s) :

CHU Lille
CNRS
Inserm
Université de Lille

Collections :

• Lille Neurosciences & Cognition (LilNCog) - U 1172
• Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576

Équipe(s) de recherche :

Biologie structurale et intégrative

Date de dépôt :

2020-02-12T15:11:29Z