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- W3186374304 abstract "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 interaction with the chaperone HSP90 and mediates cell oncogenic addiction, becomes destabilized after D-Prop treatment. HSP90 phosphorylation by PKA and its interaction with mutp53 are decreased by D-Prop, releasing mutp53 towards proteasomal degradation. Furthermore, a single daily dose of D-Prop reproduces most of these effects in xenografts of aggressive gallbladder cancerous G-415 cells expressing GOF R282W mutp53, resulting in reduced tumor growth and extended mice survival. D-Prop then emerges as an old drug endowed with a novel therapeutic potential against EGFR- and mutp53-driven tumor traits that are common to a large variety of cancers." @default.
- W3186374304 created "2021-08-02" @default.
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- W3186374304 date "2021-07-20" @default.
- W3186374304 modified "2023-10-13" @default.
- W3186374304 title "D-Propranolol Impairs EGFR Trafficking and Destabilizes Mutant p53 Counteracting AKT Signaling and Tumor Malignancy" @default.
- W3186374304 cites W1533529630 @default.
- W3186374304 cites W1591934633 @default.
- W3186374304 cites W1964321121 @default.
- W3186374304 cites W1969117282 @default.
- W3186374304 cites W1974833672 @default.
- W3186374304 cites W1977297781 @default.
- W3186374304 cites W1977582100 @default.
- W3186374304 cites W1988142400 @default.
- W3186374304 cites W1988921872 @default.
- W3186374304 cites W1991680301 @default.
- W3186374304 cites W1992273782 @default.
- W3186374304 cites W1995068068 @default.
- W3186374304 cites W1999821871 @default.
- W3186374304 cites W2004760419 @default.
- W3186374304 cites W2005155951 @default.
- W3186374304 cites W2006585409 @default.
- W3186374304 cites W2010618491 @default.
- W3186374304 cites W2017979260 @default.
- W3186374304 cites W2024502310 @default.
- W3186374304 cites W2035104343 @default.
- W3186374304 cites W2060444655 @default.
- W3186374304 cites W2061902990 @default.
- W3186374304 cites W2068322045 @default.
- W3186374304 cites W2075676198 @default.
- W3186374304 cites W2076185491 @default.
- W3186374304 cites W2080729278 @default.
- W3186374304 cites W2083663335 @default.
- W3186374304 cites W2084831115 @default.
- W3186374304 cites W2085263133 @default.
- W3186374304 cites W2087350855 @default.
- W3186374304 cites W2092539339 @default.
- W3186374304 cites W2096658459 @default.
- W3186374304 cites W2116504572 @default.
- W3186374304 cites W2118081022 @default.
- W3186374304 cites W2119748249 @default.
- W3186374304 cites W2124733101 @default.
- W3186374304 cites W2138018274 @default.
- W3186374304 cites W2138897323 @default.
- W3186374304 cites W2144963939 @default.
- W3186374304 cites W2145206503 @default.
- W3186374304 cites W2147960762 @default.
- W3186374304 cites W2155274044 @default.
- W3186374304 cites W2161648012 @default.
- W3186374304 cites W2163525606 @default.
- W3186374304 cites W2201245685 @default.
- W3186374304 cites W2236415406 @default.
- W3186374304 cites W2255416290 @default.
- W3186374304 cites W2346627954 @default.
- W3186374304 cites W2534288116 @default.
- W3186374304 cites W2584013904 @default.
- W3186374304 cites W2598705813 @default.
- W3186374304 cites W2724797371 @default.
- W3186374304 cites W2736315476 @default.
- W3186374304 cites W2751381819 @default.
- W3186374304 cites W2752942423 @default.
- W3186374304 cites W2759444489 @default.
- W3186374304 cites W2760246662 @default.
- W3186374304 cites W2765694924 @default.
- W3186374304 cites W2767299005 @default.
- W3186374304 cites W2767336741 @default.
- W3186374304 cites W2769423727 @default.
- W3186374304 cites W2782116474 @default.
- W3186374304 cites W2786714651 @default.
- W3186374304 cites W2793273918 @default.
- W3186374304 cites W2794743556 @default.
- W3186374304 cites W2806752994 @default.
- W3186374304 cites W2807919544 @default.
- W3186374304 cites W2808286046 @default.
- W3186374304 cites W2883443537 @default.
- W3186374304 cites W2892339961 @default.
- W3186374304 cites W2904049988 @default.
- W3186374304 cites W2938279459 @default.
- W3186374304 cites W2938676614 @default.
- W3186374304 cites W2943713292 @default.
- W3186374304 cites W2955225750 @default.
- W3186374304 cites W2957658998 @default.
- W3186374304 cites W2966197500 @default.