Titre :

Nerve growth factor receptor TrkA signaling in breast cancer cells involves Ku70 to prevent apoptosis.

Auteur(s) :

Com, Emmanuelle [Auteur]
Signalisation des facteurs de croissance dans le cancer du sein. Protéomique fonctionnelle
Groupe d'Etude de la Reproduction Chez l'Homme et les Mammiferes [GERHM]
Lagadec, Chann [Auteur]
Signalisation des facteurs de croissance dans le cancer du sein. Protéomique fonctionnelle
Page, Adeline [Auteur]
Belkoura, Ikram [Auteur]
Signalisation des facteurs de croissance dans le cancer du sein. Protéomique fonctionnelle
Slomianny, Christian [Auteur]
Rôle des canaux ioniques membranaires et du calcium intracellulaire dans la physiopathologie de la prostate
Spencer, Ambre [Auteur]
Laboratoire de Biologie Moléculaire de la Cellule [LBMC]
Hammache, Djilali [Auteur]
Laboratoire de Biologie Moléculaire de la Cellule [LBMC]
Rudkin, Brian B [Auteur]
Laboratoire de Biologie Moléculaire de la Cellule [LBMC]
Hondermarck, Hubert [Auteur]
Signalisation des facteurs de croissance dans le cancer du sein. Protéomique fonctionnelle

Titre de la revue :

Molecular and Cellular Proteomics

Pagination :

1842-54

Éditeur :

American Society for Biochemistry and Molecular Biology

Date de publication :

2007-11

ISSN :

1535-9476

Mot(s)-clé(s) :

Apoptosis
Cell Line
Immunoprecipitation
Receptor

Mot(s)-clé(s) en anglais :

Amino Acid Sequence
Antigens
Nuclear
Breast Neoplasms
Tumor
DNA-Binding Proteins
Green Fluorescent Proteins
Humans
Molecular Sequence Data
Nerve Growth Factor
RNA Interference
trkA
Signal Transduction

Discipline(s) HAL :

Sciences du Vivant [q-bio]/Cancer

Résumé en anglais : [en]

The nerve growth factor (NGF)-tyrosine kinase receptor TrkA plays a critical role in various neuronal and non-neuronal cell types by regulating cell survival, differentiation, and proliferation. In breast cancer cells, ...
Lire la suite >The nerve growth factor (NGF)-tyrosine kinase receptor TrkA plays a critical role in various neuronal and non-neuronal cell types by regulating cell survival, differentiation, and proliferation. In breast cancer cells, TrkA stimulation results in the activation of cellular growth, but downstream signaling largely remains to be described. Here we used a proteomics-based approach to identify partners involved in TrkA signaling in breast cancer cells. Wild type and modified TrkA chimeric constructs with green fluorescent protein were transfected in MCF-7 cells, and co-immunoprecipitated proteins were separated by SDS-PAGE before nano-LC-MS/MS analysis. Several TrkA putative signaling partners were identified among which was the DNA repair protein Ku70, which is increasingly reported for its role in cell survival and carcinogenesis. Physiological interaction of Ku70 with endogenous TrkA was induced upon NGF stimulation in non-transfected cells, and co-localization was observed with confocal microscopy. Mass spectrometry analysis and Western blotting of phosphotyrosine immunoprecipitates demonstrated the induction of Ku70 tyrosine phosphorylation upon NGF stimulation. Interestingly no interaction between TrkA and Ku70 was detected in PC12 cells in the absence or presence of NGF, suggesting that it is not involved in the initiation of neuronal differentiation. In breast cancer cells, RNA interference indicated that whereas Ku70 depletion had no direct effect on cell survival, it induced a strong potentiation of apoptosis in TrkA-overexpressing cells. In conclusion, TrkA signaling appears to be proapoptotic in the absence of Ku70, and this protein might therefore play a role in the long time reported ambivalence of tyrosine kinase receptors that can exhibit both anti- and eventually proapoptotic activities.Lire moins >

Langue :

Anglais

Vulgarisation :

Non

Collections :

• Cancer Heterogeneity, Plasticity and Resistance to Therapies (CANTHER) - UMR 9020 - UMR 1277

Source :

Harvested from HAL