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

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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.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.issn 2072-6694
dc.identifier.uri http://hdl.handle.net/10230/54399
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.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.uri http://creativecommons.org/licenses/by/4.0/
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.identifier.doi http://dx.doi.org/10.3390/cancers14102562
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.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion

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