Cell plasticity-related phenotypes and taxanes resistance in castration-resistant prostate cáncer

Jiménez, Natalia; Reig, Òscar; Montalbo, Ruth; Milà-Guasch, Maria; Nadal-Dieste, Lluis; Castellano, Giancarlo; Lozano, Juan José; Victoria, Iván; Font, Albert; Rodriguez-Vida, Alejo; Carles, Joan; Suárez, Cristina; Doménech, Montserrat; Sala-González, Núria; Fernández, Pedro Luís; Rodríguez-Carunchio, Leonardo; Díaz, Sherley; Prat, Aleix; Marín-Aguilera, Mercedes; Mellado, Begoña

Cell plasticity-related phenotypes and taxanes resistance in castration-resistant prostate cáncer

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dc.contributor.author Jiménez, Natalia
dc.contributor.author Reig, Òscar
dc.contributor.author Montalbo, Ruth
dc.contributor.author Milà-Guasch, Maria
dc.contributor.author Nadal-Dieste, Lluis
dc.contributor.author Castellano, Giancarlo
dc.contributor.author Lozano, Juan José
dc.contributor.author Victoria, Iván
dc.contributor.author Font, Albert
dc.contributor.author Rodriguez-Vida, Alejo
dc.contributor.author Carles, Joan
dc.contributor.author Suárez, Cristina
dc.contributor.author Doménech, Montserrat
dc.contributor.author Sala-González, Núria
dc.contributor.author Fernández, Pedro Luís
dc.contributor.author Rodríguez-Carunchio, Leonardo
dc.contributor.author Díaz, Sherley
dc.contributor.author Prat, Aleix
dc.contributor.author Marín-Aguilera, Mercedes
dc.contributor.author Mellado, Begoña
dc.date.accessioned 2021-07-12T06:29:06Z
dc.date.available 2021-07-12T06:29:06Z
dc.date.issued 2020
dc.description.abstract The prostatic tumor cells plasticity is involved in resistance to hormone-therapy, allowing these cells to survive despite androgen receptor inhibition. However, its role in taxanes resistance has not been fully established. Gene expression of plasticity-related phenotypes such as epithelial-mesenchymal transition (EMT), stem cell-like and neuroendocrine (NE) phenotypes was studied in vitro, in silico, in circulating tumor cells (CTCs) (N=22) and in tumor samples (N=117) from taxanes-treated metastatic castration-resistant prostate cancer (mCRPC) patients. Docetaxel (D)-resistant cells presented a more pronounced EMT phenotype than cabazitaxel (CZ)-resistant cells. In silico analysis revealed ESRP1 down-regulation in taxane-exposed mCRPC samples. Cell plasticity-related changes occurred in CTCs after taxanes treatment. Tumor EMT phenotype was associated with lower PSA progression-free survival (PFS) to D (P<0.001), and better to CZ (P=0.002). High ESRP1 expression was independently associated with longer PSA-PFS (P<0.001) and radiologic-PFS (P=0.001) in D and shorter PSA-PFS in the CZ cohort (P=0.041). High SYP expression was independently associated with lower PSA-PFS in D (P=0.003) and overall survival (OS) in CZ (P=0.002), and high EZH2 expression was associated with adverse OS in D-treated patients (P=0.013). In conclusion, EMT profile in primary tumor is differentially associated with D or CZ benefit and NE dedifferentiation correlates with adverse taxanes clinical outcome.
dc.format.mimetype application/pdf
dc.identifier.citation Jiménez N, Reig Ò, Montalbo R, Milà-Guasch M, Nadal-Dieste L, Castellano G, et al. Cell plasticity-related phenotypes and taxanes resistance in castration-resistant prostate càncer. Front Oncol. 2020 Nov 2; 10: 594023. DOI: 10.3389/fonc.2020.594023
dc.identifier.doi http://dx.doi.org/10.3389/fonc.2020.594023
dc.identifier.issn 2234-943X
dc.identifier.uri http://hdl.handle.net/10230/48155
dc.language.iso eng
dc.publisher Frontiers
dc.rights Copyright © 2020 Jiménez, Reig, Montalbo, Milà-Guasch, Nadal-Dieste, Castellano, Lozano, Victoria, Font, Rodríguez-Vida, Carles, Suárez, Domènech, Sala-González, Fernàndez, Rodríguez-Carunchio, Díaz, Prat, Marín-Aguilera and Mellado. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) http://creativecommons.org/licenses/by/4.0/. The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.subject.keyword EMT—epithelial-mesenchymal transition
dc.subject.keyword Cabazitaxel
dc.subject.keyword Castration-resistant prostate cancer
dc.subject.keyword Cell plasticity
dc.subject.keyword Docetaxel
dc.subject.keyword Neuroendocrine
dc.subject.keyword Taxanes resistance
dc.title Cell plasticity-related phenotypes and taxanes resistance in castration-resistant prostate cáncer
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/publishedVersion

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