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Your search keyword '"Farré L"' showing total 3 results
Start Over Author "Farré L" Publisher nature pub. group
3 results on '"Farré L"'

1. SMARCA4 deficient tumours are vulnerable to KDM6A/UTX and KDM6B/JMJD3 blockade.

Author

Romero OA, Vilarrubi A, Alburquerque-Bejar JJ, Gomez A, Andrades A, Trastulli D, Pros E, Setien F, Verdura S, Farré L, Martín-Tejera JF, Llabata P, Oaknin A, Saigi M, Piulats JM, Matias-Guiu X, Medina PP, Vidal A, Villanueva A, and Sanchez-Cespedes M

Subjects
Animals, Antineoplastic Agents pharmacology, Benzazepines pharmacology, Benzazepines therapeutic use, Cell Line, Tumor, Cell Survival drug effects, DNA Helicases metabolism, Drug Resistance, Neoplasm drug effects, Gene Expression, Histone Deacetylase Inhibitors pharmacology, Histone Deacetylase Inhibitors therapeutic use, Histone Demethylases genetics, Histone Demethylases metabolism, Histones metabolism, Humans, Jumonji Domain-Containing Histone Demethylases genetics, Jumonji Domain-Containing Histone Demethylases metabolism, Mice, Neoplasms metabolism, Nuclear Proteins metabolism, Pyrimidines pharmacology, Pyrimidines therapeutic use, Transcription Factors metabolism, Transcriptional Activation, Antineoplastic Agents therapeutic use, DNA Helicases deficiency, Histone Demethylases antagonists & inhibitors, Jumonji Domain-Containing Histone Demethylases antagonists & inhibitors, Neoplasms drug therapy, Nuclear Proteins deficiency, Transcription Factors deficiency
Abstract

Despite the genetic inactivation of SMARCA4, a core component of the SWI/SNF-complex commonly found in cancer, there are no therapies that effectively target SMARCA4-deficient tumours. Here, we show that, unlike the cells with activated MYC oncogene, cells with SMARCA4 inactivation are refractory to the histone deacetylase inhibitor, SAHA, leading to the aberrant accumulation of H3K27me3. SMARCA4-mutant cells also show an impaired transactivation and significantly reduced levels of the histone demethylases KDM6A/UTX and KDM6B/JMJD3, and a strong dependency on these histone demethylases, so that its inhibition compromises cell viability. Administering the KDM6 inhibitor GSK-J4 to mice orthotopically implanted with SMARCA4-mutant lung cancer cells or primary small cell carcinoma of the ovary, hypercalcaemic type (SCCOHT), had strong anti-tumour effects. In this work we highlight the vulnerability of KDM6 inhibitors as a characteristic that could be exploited for treating SMARCA4-mutant cancer patients., (© 2021. The Author(s).)

Published
2021
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2. XPO1 inhibitors represent a novel therapeutic option in Adult T-cell Leukemia, triggering p53-mediated caspase-dependent apoptosis.

Author

Boons E, Nogueira TC, Dierckx T, Menezes SM, Jacquemyn M, Tamir S, Landesman Y, Farré L, Bittencourt A, Kataoka K, Ogawa S, Snoeck R, Andrei G, Van Weyenbergh J, and Daelemans D

Subjects
Antineoplastic Agents pharmacology, Cell Line, Tumor, Humans, Karyopherins metabolism, Leukemia-Lymphoma, Adult T-Cell metabolism, Receptors, Cytoplasmic and Nuclear metabolism, Exportin 1 Protein, Apoptosis drug effects, Hydrazines pharmacology, Karyopherins antagonists & inhibitors, Leukemia-Lymphoma, Adult T-Cell drug therapy, Receptors, Cytoplasmic and Nuclear antagonists & inhibitors, Triazoles pharmacology, Tumor Suppressor Protein p53 metabolism
Published
2021
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3. The transcribed pseudogene RPSAP52 enhances the oncofetal HMGA2-IGF2BP2-RAS axis through LIN28B-dependent and independent let-7 inhibition.

Author

Oliveira-Mateos C, Sánchez-Castillo A, Soler M, Obiols-Guardia A, Piñeyro D, Boque-Sastre R, Calleja-Cervantes ME, Castro de Moura M, Martínez-Cardús A, Rubio T, Pelletier J, Martínez-Iniesta M, Herrero-Martín D, Tirado OM, Gentilella A, Villanueva A, Esteller M, Farré L, and Guil S

Subjects
Animals, Breast Neoplasms genetics, Breast Neoplasms metabolism, Breast Neoplasms therapy, Cell Line, Cell Line, Tumor, Female, Gene Expression Profiling methods, HMGA2 Protein genetics, HMGA2 Protein metabolism, Humans, Kaplan-Meier Estimate, MCF-7 Cells, Mice, Nude, Proteins metabolism, RNA-Binding Proteins metabolism, RNAi Therapeutics methods, Transcription, Genetic, Tumor Burden genetics, Xenograft Model Antitumor Assays methods, ras Proteins genetics, ras Proteins metabolism, Gene Expression Regulation, Neoplastic, MicroRNAs genetics, Proteins genetics, Pseudogenes genetics, RNA-Binding Proteins genetics, Signal Transduction genetics
Abstract

One largely unknown question in cell biology is the discrimination between inconsequential and functional transcriptional events with relevant regulatory functions. Here, we find that the oncofetal HMGA2 gene is aberrantly reexpressed in many tumor types together with its antisense transcribed pseudogene RPSAP52. RPSAP52 is abundantly present in the cytoplasm, where it interacts with the RNA binding protein IGF2BP2/IMP2, facilitating its binding to mRNA targets, promoting their translation by mediating their recruitment on polysomes and enhancing proliferative and self-renewal pathways. Notably, downregulation of RPSAP52 impairs the balance between the oncogene LIN28B and the tumor suppressor let-7 family of miRNAs, inhibits cellular proliferation and migration in vitro and slows down tumor growth in vivo. In addition, high levels of RPSAP52 in patient samples associate with a worse prognosis in sarcomas. Overall, we reveal the roles of a transcribed pseudogene that may display properties of an oncofetal master regulator in human cancers.

Published
2019
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