7520

XRCC5

X-ray repair complementing defective repair in Chinese hamster cells 5 (double-strand-break rejoining);XRCC5;X-ray repair complementing defective repair in Chinese hamster cells 5 (double-strand-break rejoining)

86 kDa subunit of Ku antigen|ATP-dependent DNA helicase 2 subunit 2|ATP-dependent DNA helicase II 80 kDa subunit|CTC box-binding factor 85 kDa subunit|CTC85|CTCBF|DNA repair protein XRCC5|Ku autoantigen, 80kDa|Ku86 autoantigen related protein 1|TLAA|X-ray

2q35

protein-coding

PURPOSE: 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. EXPERIMENTAL DESIGN: 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 AND CLINICAL RELEVANCE: 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.