TY - JOUR
T1 - Role of c-Src and focal adhesion kinase in progression and metastasis of estrogen receptor-positive breast cancer
AU - Planas-Silva, Maricarmen D.
AU - Bruggeman, Richard D.
AU - Grenko, Ronald T.
AU - Stanley Smith, J.
N1 - Funding Information:
We thank Kent Vrana and Elliot Vesell for comments on the manuscript, and Kecia Hamilton for technical assistance. M.D. Planas-Silva is recipient of a Career Developmental Award from the US Army Medical Research and Materiel Command Breast Cancer Research Program, DAMD 17-02-1-0540. This project is funded, in part, under a grant with the Pennsylvania Department of Health using Tobacco Settlement Funds. The Department specifically disclaims responsibility for any analyses, interpretations or conclusions.
PY - 2006/3/3
Y1 - 2006/3/3
N2 - The non-receptor tyrosine kinases c-Src and focal adhesion kinase (Fak) mediate signal transduction pathways that regulate cell proliferation, survival, invasion, and metastasis. Here, we investigated whether c-Src and Fak are activated during progression of hormone-dependent breast cancer. Maximally active c-Src was overexpressed in a subset of tamoxifen-resistant variants and in metastases of recurrent hormone-treated breast cancer. Active Fak was also frequently observed in these tumors. We also show that estrogen receptor (ER) can bind to Fak and that estrogen can modulate Fak autophosphorylation supporting a cross-talk between these two pathways. Inhibition of c-Src activity blocked proliferation of all tamoxifen-resistant variants, suggesting that inhibitors of c-Src-Fak activity may delay or prevent progression and metastasis of ER-positive tumors. These studies also raise the possibility that fully active forms of c-Src and Fak in breast tumors may be biomarkers to predict tamoxifen resistance and/or risk of recurrence in ER-positive breast cancer.
AB - The non-receptor tyrosine kinases c-Src and focal adhesion kinase (Fak) mediate signal transduction pathways that regulate cell proliferation, survival, invasion, and metastasis. Here, we investigated whether c-Src and Fak are activated during progression of hormone-dependent breast cancer. Maximally active c-Src was overexpressed in a subset of tamoxifen-resistant variants and in metastases of recurrent hormone-treated breast cancer. Active Fak was also frequently observed in these tumors. We also show that estrogen receptor (ER) can bind to Fak and that estrogen can modulate Fak autophosphorylation supporting a cross-talk between these two pathways. Inhibition of c-Src activity blocked proliferation of all tamoxifen-resistant variants, suggesting that inhibitors of c-Src-Fak activity may delay or prevent progression and metastasis of ER-positive tumors. These studies also raise the possibility that fully active forms of c-Src and Fak in breast tumors may be biomarkers to predict tamoxifen resistance and/or risk of recurrence in ER-positive breast cancer.
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U2 - 10.1016/j.bbrc.2005.12.164
DO - 10.1016/j.bbrc.2005.12.164
M3 - Article
C2 - 16412380
AN - SCOPUS:31044447246
SN - 0006-291X
VL - 341
SP - 73
EP - 81
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -
