@article{10902/19263,
year = {2020},
month = {5},
url = {http://hdl.handle.net/10902/19263},
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.},
organization = {Acknowledgments: Our laboratories are supported by Instituto de Salud Carlos III, Spain, with FEDER cofinancing (grants PI14-00435 and PI17-00576 to PP); by Ministerio de Economía; Industria y Competitividad (MINECO) of Spain (grant SAF2017-84125-R to F.M. and SAF2017-87301-R (to M.L.M-C); by CIBERCV-Instituto de Salud Carlos III, Spain (grant CB16/11/00278 to F.M, co-funded with European Regional Development Fund-FEDER contribution); by Programa de Actividades en Biomedicina de la Comunidad de Madrid-B2017/BMD-3671-INFLAMUNE and Fundación Ramón Areces to F.M.); and by Asociación Española contra el Cáncer, Canceres raros, La Caixa Foundation, and Ayudas Fundación BBVA (to M.L.M-C).We also acknowledge institutional support to the CBMSO from Fundación Ramón Areces and MINECO (SEV-2016-0644) for the Severo Ochoa Excellence Accreditation.},
publisher = {MDPI},
publisher = {Cancers (Basel)
. 2020 May 13;12(5):1216},
title = {GRK2-Dependent HuR Phosphorylation Regulates HIF1? Activation under Hypoxia or Adrenergic Stress},
author = {Reglero, Clara and Lafarga Berciano, Vanesa and Rivas, Veronica and Albitre, Ángela and Ramos, Paula and Berciano, Susana and Tapia Martínez, Olga and Martínez Chantar, María L. and Mayor, Federico and Penela, Petronila},
}