HEИндивидуална стипендия2024–2026

NutFLirsFA · NUTRIENT FLUCTUATIONS AND THE INTEGRATIVE STRESS RESPONSE AS METABOLIC CELL FATE DETERMINANTS IN B CELL LYMPHOMA

„Хоризонт Европа“ — Действия „Мария Склодовска-Кюри“

Период: 2024-09-01 → 2026-08-31
Финансиране от ЕС: 165 313 €
Участници: 1
Схема: HORIZON-TMA-MSCA-PF-EF

Линиите свързват координатора с партньорите.

Накратко на български

Връзката между мастните киселини, стресовите реакции на клетката и протеина MITF се проучва при B-клеточни лимфоми. Разбирането на тези процеси помага да се разбере как се променя идентичността на клетките и как се развива ракът.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

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 factor MITF, known to regulate 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 a dedifferentiated phenotype 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 changes in 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, we will establish if and how MITF and FA composition, along with the ISR, control B-cell transitions (Objective 1) and impact lymphomagenesis (Objective 2). I propose that an abnormal ISR and MITF/SCD1 deregulation corrupt the B-cell differentiation process, contributing to lymphomagenesis. This proposal, by means of using cutting edge technology combining in vivo and in vitro approaches, 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.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

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.

Оригинален текст от CORDIS (на английски).

Участници

FUNDACION SECTOR PUBLICO ESTATAL CENTRO NACIONAL INVESTIGACIONES ONCOLOGICAS CARLOS III · MadridКоординаторИспания