A Dual Role for FADD in Human Precursor T-Cell Neoplasms

Autor: José Luis Marín-Rubio, Laura Vela-Martín, Jack Gudgeon, Eduardo Pérez-Gómez, Frances R. Sidgwick, Matthias Trost, Debbie L. Cunningham, Javier Santos, José Fernández-Piqueras, María Villa-Morales
Přispěvatelé: UAM. Departamento de Biología
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: International Journal of Molecular Sciences; Volume 23; Issue 23; Pages: 15157
ISSN: 1422-0067
DOI: 10.3390/ijms232315157
Popis: A reduction in FADD levels has been reported in precursor T-cell neoplasms and other tumor types. Such reduction would impact on the ability of tumor cells to undergo apoptosis and has been associated with poor clinical outcomes. However, FADD is also known to participate in non-apoptotic functions, but these mechanisms are not well-understood. Linking FADD expression to the severity of precursor T-cell neoplasms could indicate its use as a prognostic marker and may open new avenues for targeted therapeutic strategies. Using transcriptomic and clinical data from patients with precursor T-cell neoplasms, complemented by in vitro analysis of cellular functions and by high-throughput interactomics, our results allow us to propose a dual role for FADD in precursor T-cell neoplasms, whereby resisting cell death and chemotherapy would be a canonical consequence of FADD deficiency in these tumors, whereas deregulation of the cellular metabolism would be a relevant non-canonical function in patients expressing FADD. These results reveal that evaluation of FADD expression in precursor T-cell neoplasms may aid in the understanding of the biological processes that are affected in the tumor cells. The altered biological processes can be of different natures depending on the availability of FADD influencing its ability to exert its canonical or non-canonical functions. Accordingly, specific therapeutic interventions would be needed in each case
This research was funded by grants from Spanish Ministry of Economy and Competitiveness (SAF2015-70561 MINECO/FEDER, UE to J.F.-P./M.V.-M.; PI20/00590 MINECO/FEDER to E.P.- G.), Spanish Ministry of Science, Innovation and Universities (RTI2018-093330-B-I00; MCIU/FEDER, EU to J.F.-P. and J.S.); Fundación Ramón Areces (CIVP19S7917 to J.F.-P.); the Autonomous Community of Madrid, Spain (B2017/BMD-3778; LINFOMAS-CM to J.F.-P.), the Instituto de Salud Carlos III (ACCI-CIBERER-17 ISCIII to J.F.-P.), and Scientific Foundation of Asociación Española Contra el Cáncer (AECC, 2018; PROYE18054PIRI to J.F.-P). J.L.M.-R. was funded by a predoctoral fellowship from Spanish Ministry of Education, Culture and Sports (FPU13/00338); mass spectrometry studies were performed at University of Birmingham with the help of travel fellowships by the Federation of European Biochemical Societies (FEBS), Journal of Cell Science (JCSTF-161105) and the European Association for Cancer Research (EACR, Ref. #571). Institutional grants from the Fundación Ramón Areces and Banco de Santander to the CBMSO are also acknowledged
Databáze: OpenAIRE
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