Ku86 is important for TrkA overexpression-induced breast cancer cell invasion.
OBJECTIVE
We have recently shown that breast tumors express high levels of TrkA compared with normal breast tissues, with TrkA overexpression enhancing breast cancer cell invasion in vitro and metastasis in animal models. In this study, we tried to identify molecules involved in TrkA overexpression-mediated biological effects in breast cancer cells.


METHODS
We used a proteomic-based approach to identify proteins involved in TrkA overexpression-stimulated invasion of MDA-MB-231 breast cancer cells. Proteins from control and TrkA overexpressing cells were separated using a cup-loading two-dimensional electrophoresis system before MALDI and LC-MS/MS mass spectrometry analysis.


RESULTS
Among several putative regulated proteins, Ku86 was found increased in TrkA overexpressing cells. Moreover, Ku86 was co-immunoprecipitated with TrkA, suggesting the interaction of these two proteins in TrkA overexpressing cells. Interestingly, inhibition with small-interfering RNA and neutralizing antibodies showed that Ku86 was required for TrkA-stimulated cell invasion.


CONCLUSIONS
These data allowed the identification of Ku86 as a new player involved in metastasis in breast cancer cells. Our findings suggest that TrkA and its down stream signaling pathways should be regarded as potential new targets for the development of future breast cancer therapy.
Signalisation des facteurs de croissance dans le cancer du sein. Proteomique fonctionnelle, Université Lille 1, Villeneuve d'Ascq, France.
Chann
C
Lagadec
Rodrigue
R
Romon
Christophe
C
Tastet
Samuel
S
Meignan
Emmanuelle
E
Com
Adeline
A
Page
Gabriel
G
Bidaux
Hubert
H
Hondermarck
Xuefen
X
Le Bourhis
D034961:Antigens, Nuclear / Q000096:biosynthesis; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D004265:DNA Helicases / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D005260:Female; D006801:Humans; D000072200:Ku Autoantigen; D009361:Neoplasm Invasiveness / Q000503:physiopathology*; D020917:Receptor, trkA / Q000096:biosynthesis* / Q000302:isolation & purification; D015854:Up-Regulation
D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D020917:Receptor, trkA; D004265:DNA Helicases; C106893:XRCC5 protein, human; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen