Jiménez, NataliaReig, ÒscarMontalbo, RuthMilà-Guasch, MariaNadal-Dieste, LluisCastellano, GiancarloLozano, Juan JoséVictoria, IvánFont, AlbertRodriguez-Vida, AlejoCarles, JoanSuárez, CristinaDoménech, MontserratSala-González, NúriaFernández, Pedro LuísRodríguez-Carunchio, LeonardoDíaz, SherleyPrat, AleixMarín-Aguilera, MercedesMellado, Begoña2021-07-122021-07-122020Jiménez 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.2020.5940232234-943Xhttp://hdl.handle.net/10230/48155The 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.application/pdfengCopyright © 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.info:eu-repo/semantics/articlehttp://dx.doi.org/10.3389/fonc.2020.594023EMT—epithelial-mesenchymal transitionCabazitaxelCastration-resistant prostate cancerCell plasticityDocetaxelNeuroendocrineTaxanes resistanceinfo:eu-repo/semantics/openAccess