GDF15 is an eribulin response biomarker also required for survival of DTP breast cancer cells

Mostra el registre complet Registre parcial de l'ítem

• dc.contributor.author Bellio, Chiara
• dc.contributor.author Emperador, Marta
• dc.contributor.author Castellano, Pol
• dc.contributor.author Gris-Oliver, Albert
• dc.contributor.author Canals, Francesc
• dc.contributor.author Sánchez Pla, Alexandre
• dc.contributor.author Zamora, Esther
• dc.contributor.author Arribas, Joaquín
• dc.contributor.author Saura, Cristina
• dc.contributor.author Serra, Violeta
• dc.contributor.author Tabernero Cartula, Josep
• dc.contributor.author Littlefield, Bruce A.
• dc.contributor.author Villanueva, Josep
• dc.date.accessioned 2022-10-14T06:53:30Z
• dc.date.available 2022-10-14T06:53:30Z
• dc.date.issued 2022
• dc.description.abstract Drug tolerant persister (DTP) cells enter into a reversible slow-cycling state after drug treatment. We performed proteomic characterization of the breast cancer (BC) DTP cell secretome after eribulin treatment. We showed that the growth differentiation factor 15 (GDF15) is a protein significantly over-secreted upon eribulin treatment. The biomarker potential of GDF15 was confirmed in 3D-cell culture models using BC cells lines and PDXs, as well as in a TNBC in vivo model. We also found that GDF15 is required for survival of DTP cells. Direct participation of GDF15 and its receptor GFRAL in eribulin-induction of DTPs was established by the enhanced cell killing of DTPs by eribulin seen under GDF15 and GFRAL loss of function assays. Finally, we showed that combination therapy of eribulin plus an anti-GDF15 antibody kills BC-DTP cells. Our results suggest that targeting GDF15 may help eradicate DTP cells and block the onset of acquired resistance.
• dc.format.mimetype application/pdf
• dc.identifier.citation Bellio C, Emperador M, Castellano P, Gris-Oliver A, Canals F, Sánchez-Pla A, et al. GDF15 is an eribulin response biomarker also required for survival of DTP breast cancer cells. Cancers (Basel). 2022 May 23; 14(10): 2562. DOI: 10.3390/cancers14102562
• dc.identifier.doi http://dx.doi.org/10.3390/cancers14102562
• dc.identifier.issn 2072-6694
• dc.identifier.uri http://hdl.handle.net/10230/54399
• dc.language.iso eng
• dc.publisher MDPI
• dc.rights Copyright © 2022 by Bellio C, Emperador M, Castellano P, Gris-Oliver A, Canals F, Sánchez-Pla A.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 (http://creativecommons.org/licenses/by/4.0/).
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Breast cancer (BC)
• dc.subject.keyword Drug tolerance
• dc.subject.keyword Drug tolerant persister (DTP)
• dc.subject.keyword Eribulin
• dc.subject.keyword Growth differentiation factor 15 (GDF15)
• dc.subject.keyword Secretome
• dc.title GDF15 is an eribulin response biomarker also required for survival of DTP breast cancer cells
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion