Cancers, Vol. 13, Pages 3622: D-Propranolol Impairs EGFR Trafficking and Destabilizes Mutant p53 Counteracting AKT Signaling and Tumor Malignancy
Cancers, Vol. 13, Pages 3622: D-Propranolol Impairs EGFR Trafficking and Destabilizes Mutant p53 Counteracting AKT Signaling and Tumor Malignancy
Cancers doi: 10.3390/cancers13143622
Authors:
Jonathan Barra
Javier Cerda-Infante
Lisette Sandoval
Patricia Gajardo-Meneses
Jenny F. Henriquez
Mariana Labarca
Claudia Metz
Jaime Venegas
Claudio Retamal
Claudia Oyanadel
Jorge Cancino
Andrea Soza
Mauricio A. Cuello
Juan Carlos Roa
Viviana P. Montecinos
Alfonso Gonzalez
Cancer therapy may be improved by the simultaneous interference of two or more oncogenic pathways contributing to tumor progression and aggressiveness, such as EGFR and p53. Tumor cells expressing gain-of-function (GOF) mutants of p53 (mutp53) are usually resistant to EGFR inhibitors and display invasive migration and AKT-mediated survival associated with enhanced EGFR recycling. D-Propranolol (D-Prop), the non-beta blocker enantiomer of propranolol, was previously shown to induce EGFR internalization through a PKA inhibitory pathway that blocks the recycling of the receptor. Here, we first show that D-Prop decreases the levels of EGFR at the surface of GOF mutp53 cells, relocating the receptor towards recycling endosomes, both in the absence of ligand and during stimulation with high concentrations of EGF or TGF-α. D-Prop also inactivates AKT signaling and reduces the invasive migration and viability of these mutp53 cells. Unexpectedly, mutp53 protein, which is stabilized by inter...
Source: Cancers - Category: Cancer & Oncology Authors: Jonathan Barra Javier Cerda-Infante Lisette Sandoval Patricia Gajardo-Meneses Jenny F. Henriquez Mariana Labarca Claudia Metz Jaime Venegas Claudio Retamal Claudia Oyanadel Jorge Cancino Andrea Soza Mauricio A. Cuello Juan Carlos Roa Viviana P. Montecinos Tags: Article Source Type: research
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