Blocking the epithelial-to-mesenchymal transition pathway abrogates resistance to anti-folate chemotherapy in lung cancer.

Détails

ID Serval
serval:BIB_1235E303F56F
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Blocking the epithelial-to-mesenchymal transition pathway abrogates resistance to anti-folate chemotherapy in lung cancer.
Périodique
Cell death & disease
Auteur(s)
Liang S.Q., Marti T.M., Dorn P., Froment L., Hall S.R., Berezowska S., Kocher G., Schmid R.A., Peng R.W.
ISSN
2041-4889 (Electronic)
Statut éditorial
Publié
Date de publication
16/07/2015
Peer-reviewed
Oui
Volume
6
Pages
e1824
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Résumé
Anticancer therapies currently used in the clinic often can neither eradicate the tumor nor prevent disease recurrence due to tumor resistance. In this study, we showed that chemoresistance to pemetrexed, a multi-target anti-folate (MTA) chemotherapeutic agent for non-small cell lung cancer (NSCLC), is associated with a stem cell-like phenotype characterized by an enriched stem cell gene signature, augmented aldehyde dehydrogenase activity and greater clonogenic potential. Mechanistically, chemoresistance to MTA requires activation of epithelial-to-mesenchymal transition (EMT) pathway in that an experimentally induced EMT per se promotes chemoresistance in NSCLC and inhibition of EMT signaling by kaempferol renders the otherwise chemoresistant cancer cells susceptible to MTA. Relevant to the clinical setting, human primary NSCLC cells with an elevated EMT signaling feature a significantly enhanced potential to resist MTA, whereas concomitant administration of kaempferol abrogates MTA chemoresistance, regardless of whether it is due to an intrinsic or induced activation of the EMT pathway. Collectively, our findings reveal that a bona fide activation of EMT pathway is required and sufficient for chemoresistance to MTA and that kaempferol potently regresses this chemotherapy refractory phenotype, highlighting the potential of EMT pathway inhibition to enhance chemotherapeutic response of lung cancer.
Mots-clé
Antineoplastic Agents/administration & dosage, Carcinoma, Non-Small-Cell Lung/drug therapy, Carcinoma, Non-Small-Cell Lung/genetics, Carcinoma, Non-Small-Cell Lung/pathology, Cell Line, Tumor, Drug Resistance, Neoplasm/genetics, Epithelial-Mesenchymal Transition/drug effects, Epithelial-Mesenchymal Transition/genetics, Folic Acid/metabolism, Folic Acid Antagonists/administration & dosage, Humans, Lung Neoplasms/drug therapy, Lung Neoplasms/genetics, Lung Neoplasms/pathology, Neoplasm Recurrence, Local/drug therapy, Neoplasm Recurrence, Local/genetics, Neoplasm Recurrence, Local/pathology, Signal Transduction
Pubmed
Web of science
Open Access
Oui
Création de la notice
29/06/2020 12:04
Dernière modification de la notice
30/06/2020 6:26
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