Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 2 de 2
Filtrar
Más filtros

Banco de datos
Tipo de estudio
Tipo del documento
Intervalo de año de publicación
1.
Genes Dev ; 34(11-12): 751-766, 2020 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-32273287

RESUMEN

Human cancers with activating RAS mutations are typically highly aggressive and treatment-refractory, yet RAS mutation itself is insufficient for tumorigenesis, due in part to profound metabolic stress induced by RAS activation. Here we show that loss of REDD1, a stress-induced metabolic regulator, is sufficient to reprogram lipid metabolism and drive progression of RAS mutant cancers. Redd1 deletion in genetically engineered mouse models (GEMMs) of KRAS-dependent pancreatic and lung adenocarcinomas converts preneoplastic lesions into invasive and metastatic carcinomas. Metabolic profiling reveals that REDD1-deficient/RAS mutant cells exhibit enhanced uptake of lysophospholipids and lipid storage, coupled to augmented fatty acid oxidation that sustains both ATP levels and ROS-detoxifying NADPH. Mechanistically, REDD1 loss triggers HIF-dependent activation of a lipid storage pathway involving PPARγ and the prometastatic factor CD36. Correspondingly, decreased REDD1 expression and a signature of REDD1 loss predict poor outcomes selectively in RAS mutant but not RAS wild-type human lung and pancreas carcinomas. Collectively, our findings reveal the REDD1-mediated stress response as a novel tumor suppressor whose loss defines a RAS mutant tumor subset characterized by reprogramming of lipid metabolism, invasive and metastatic progression, and poor prognosis. This work thus provides new mechanistic and clinically relevant insights into the phenotypic heterogeneity and metabolic rewiring that underlies these common cancers.


Asunto(s)
Metabolismo de los Lípidos/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Proteínas ras/genética , Animales , Línea Celular Tumoral , Progresión de la Enfermedad , Ácidos Grasos/metabolismo , Células HEK293 , Humanos , Ratones , Ratones SCID , Mutación , Oxidación-Reducción
2.
Bioresour Technol ; 96(8): 949-53, 2005 May.
Artículo en Inglés | MEDLINE | ID: mdl-15627566

RESUMEN

Modified solid-state fermentation (MSSF) of tannin-rich substrate yielding tannase and gallic acid was carried out using a co-culture of the filamentous fungi, Rhizopus oryzae (RO IIT RB-13, NRRL 21498) and Aspergillus foetidus (GMRB013 MTCC 3557). Powdered fruits of Terminalia chebula and powdered pod cover of Caesalpinia digyna was used in the process and the different process parameters for maximum production of tannase and gallic acid by co-culture method were optimized through media engineering. MSSF was carried out at the optimum conditions of 30 degrees C and 80% relative humidity. The optimal pH and incubation period was 5.0 and 48 h respectively. Through the co-culture technique the maximum yield of tannase and gallic acid was found to be 41.3 U/ml and 94.8% respectively.


Asunto(s)
Reactores Biológicos , Ácido Gálico/análisis , Taninos/metabolismo , Fermentación , Hongos , Concentración de Iones de Hidrógeno
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA