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Ku86 is important for TrkA overexpression‐induced breast cancer cell invasion
Author(s) -
Lagadec Chann,
Romon Rodrigue,
Tastet Christophe,
Meignan Samuel,
Com Emmanuelle,
Page Adeline,
Bidaux Gabriel,
Hondermarck Hubert,
Le Bourhis Xuefen
Publication year - 2010
Publication title -
proteomics – clinical applications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.948
H-Index - 54
eISSN - 1862-8354
pISSN - 1862-8346
DOI - 10.1002/prca.200900148
Subject(s) - tropomyosin receptor kinase a , breast cancer , cancer research , metastasis , biology , low affinity nerve growth factor receptor , cancer cell , cell , cancer , microbiology and biotechnology , chemistry , receptor , nerve growth factor , biochemistry , genetics
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.