NutFLirsFA
Financiado
NUTRIENT FLUCTUATIONS AND THE INTEGRATIVE STRESS RESPONSE AS METABOLIC CELL FATE...
NUTRIENT FLUCTUATIONS AND THE INTEGRATIVE STRESS RESPONSE AS METABOLIC CELL FATE DETERMINANTS IN B CELL LYMPHOMA
Metabolic reprogramming enables cells to adopt different phenotypes, providing flexibility in response to environmental stress, of particular relevance during tumour development. I recently demonstrated that the transcription fact...
Metabolic reprogramming enables cells to adopt different phenotypes, providing flexibility in response to environmental stress, of particular relevance during tumour development. I recently demonstrated that the transcription factor MITF, known regulator of cell transitions in melanoma, controls the expression of the fatty acid (FA) desaturase SCD1. The MITF/SCD1 axis maintains cell differentiation, while its suppression by starvation-induced Integrative Stress Response (ISR) originates dedifferentiation and melanoma progression. Our findings support that metabolic rewiring and phenotype switching are interconnected events that govern tumour progression.
As in melanoma, B-cell differentiation depends on MITF activity, FA metabolism and a dynamic modulation of ISR, but weather an interplay among these factors dictates B-cell fate is still unknown. Importantly, MITF is regulated by mTORC1/RagGTPase signalling, pathway frequently mutated in B-cell lymphomas. I hypothesize that the ISR/MITF axis and FA metabolism enable normal and pathological B cells to adapt to stress, and critically licenses switches in phenotypic identity and B-cell behaviour. Thus, I will establish if and how MITF and FA composition control B-cell transitions and impact lymphomagenesis, along with its regulation by the ISR. We propose that abnormal ISR and MITF/SCD1 deregulation corrupts B-cell differentiation process, contributing to lymphomagenesis.
This proposal aims at shedding light on the interplay between nutritional signals and stress-related cellular responses that precipitate cancer cell transitions through the regulation of specific transcriptional programs controlling metabolic rewiring.
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Duración del proyecto: 40 meses
Fecha Inicio: 2023-04-28
Fecha Fin: 2026-08-31
Fecha Fin: 2026-08-31
Línea de financiación: concedida
El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2023-04-28
Línea de financiación objetivo
El proyecto se financió a través de la siguiente ayuda:
HORIZON-MSCA-2022-PF-01-01:
MSCA Postdoctoral Fellowships 2022
Cerrada
hace 2 años
Presupuesto
El presupuesto total del proyecto asciende a
165K€
Líder del proyecto
FUNDACION SECTOR PUBLICO ESTATAL CENTRO NACIO...
No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico
TRL
4-5
18M
Perfil tecnológico
TRL
4-5
18M