Buscar

 Detalle_Publicacion

GRK2-Dependent HuR Phosphorylation Regulates HIF1? Activation under Hypoxia or Adrenergic Stress

Abstract: Adaptation to hypoxia is a common feature in solid tumors orchestrated by oxygen-dependent and independent upregulation of the hypoxia-inducible factor-1? (HIF-1?). We unveiled that G protein-coupled receptor kinase (GRK2), known to be overexpressed in certain tumors, fosters this hypoxic pathway via phosphorylation of the mRNA-binding protein HuR, a central HIF-1? modulator. GRK2-mediated HuR phosphorylation increases the total levels and cytoplasmic shuttling of HuR in response to hypoxia, and GRK2-phosphodefective HuR mutants show defective cytosolic accumulation and lower binding to HIF-1? mRNA in hypoxic Hela cells. Interestingly, enhanced GRK2 and HuR expression correlate in luminal breast cancer patients. GRK2 also promotes the HuR/HIF-1? axis and VEGF-C accumulation in normoxic MCF7 breast luminal cancer cells and is required for the induction of HuR/HIF1-? in response to adrenergic stress. Our results point to a relevant role of the GRK2/HuR/HIF-1? module in the adaptation of malignant cells to tumor microenvironment-related stresses.

 Fuente: Cancers (Basel) . 2020 May 13;12(5):1216

Editorial: MDPI

 Fecha de publicación: 01/05/2020

Nº de páginas: 21

Tipo de publicación: Artículo de Revista

 DOI: 10.3390/cancers12051216

ISSN: 2072-6694

Proyecto español: SAF2017-84125-R ; SAF2017-87301-R

Url de la publicación: http://dx.doi.org/10.3390/cancers12051216

Autores/as

REGLERO, CLARA

VANESA LAFARGA BERCIANO

RIVAS, VERONICA

ALBITRE, ÁNGELA

RAMOS, PAULA

BERCIANO, SUSANA

OLGA TAPIA MARTINEZ

MARTÍNEZ CHANTAR, MARÍA L.

MAYOR, FEDERICO

PENELA, PETRONILA