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β-Catenin activity induces an RNA biosynthesis program promoting therapy resistance in T-cell acute lymphoblastic leukemia

Identificadores del recurso

García-Hernández V, Arambilet D, Guillén Y, Lobo-Jarne T, Maqueda M, Gekas C, González J, Iglesias A, Vega-García N, Sentís I, Trincado JL, Márquez-López I, Heyn H, Camós M, Espinosa L, Bigas A. β-Catenin activity induces an RNA biosynthesis program promoting therapy resistance in T-cell acute lymphoblastic leukemia. EMBO Mol Med. 2023 Feb 8;15(2):e16554. DOI: 10.15252/emmm.202216554

1757-4676

http://hdl.handle.net/10230/56039

http://dx.doi.org/10.15252/emmm.202216554

Procedència

(e-Repositori: Repositori digital de la UPF)

Fitxa

Títol:: β-Catenin activity induces an RNA biosynthesis program promoting therapy resistance in T-cell acute lymphoblastic leukemia
Tema:: Kaiso; RNA processing; T-ALL; Chemotherapy resistance; β-catenin
Descripció:: Understanding the molecular mechanisms that contribute to the appearance of chemotherapy resistant cell populations is necessary to improve cancer treatment. We have now investigated the role of β-catenin/CTNNB1 in the evolution of T-cell Acute Lymphoblastic Leukemia (T-ALL) patients and its involvement in therapy resistance. We have identified a specific gene signature that is directly regulated by β-catenin, TCF/LEF factors and ZBTB33/Kaiso in T-ALL cell lines, which is highly and significantly represented in five out of six refractory patients from a cohort of 40 children with T-ALL. By subsequent refinement of this gene signature, we found that a subset of β-catenin target genes involved with RNA-processing function are sufficient to segregate T-ALL refractory patients in three independent cohorts. We demonstrate the implication of β-catenin in RNA and protein synthesis in T-ALL and provide in vitro and in vivo experimental evidence that β-catenin is crucial for the cellular response to chemotherapy, mainly in the cellular recovery phase after treatment. We propose that combination treatments involving chemotherapy plus β-catenin inhibitors will enhance chemotherapy response and prevent disease relapse in T-ALL patients.; This work has been funded by Agencia Estatal de Investigación (SAF2016-75613-R and PID2019-104695RB-I00), Fundación AECC (GC16173697BIGA) and WCR (13-0064). VGH, DA and TL are recipients of Sara Borrell fellowship from ISCIII co-funded by the ESF+ (CD21/00145), FPI (BES-2017-080880) and AECC fellowship (POSTD21975LOBO), respectively.
Idioma:: English
Relació:: EMBO Mol Med. 2023 Feb 8;15(2):e16554; info:eu-repo/grantAgreement/ES/1PE/SAF2016-75613-R; info:eu-repo/grantAgreement/ES/2PE/PID2019-104695RB-I00
Autor/Productor:: García Hernández, Violeta; Arambilet, David; Guillén, Yolanda; Lobo-Jarne, Teresa; Maqueda, Maria; Gekas, Christos; González, Jessica; Iglesias, Arnau; Vega García, Nerea; Sentís Carreras, Inés 1990-; Trincado Alonso, Juan Luis, 1987-; Márquez-López, Ian; Heyn, Holger; Camós, Mireia; Espinosa Blay, Lluís; Bigas Salvans, Anna
Editor:: Wiley
Drets:: © 2023 The Authors. Published under the terms of the CC BY 4.0 license. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.; http://creativecommons.org/licenses/by/4.0/; info:eu-repo/semantics/openAccess
Data:: 2023
Tipo de recurso:: info:eu-repo/semantics/article; info:eu-repo/semantics/publishedVersion
Format:: application/pdf

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