Abstract
Metastasis remains a significant challenge in treating cancer. A better understanding of the molecular mechanisms underlying metastasis is needed to develop more effective treatments. Here, we show that human breast tumor biomarker miR-30c regulates invasion by targeting the cytoskeleton network genes encoding twinfilin 1 (TWF1) and vimentin (VIM). Both VIM and TWF1 have been shown to regulate epithelial-to-mesenchymal transition. Similar to TWF1, VIM also regulates F-actin formation, a key component of cellular transition to a more invasive mesenchymal phenotype. To further characterize the role of the TWF1 pathway in breast cancer, we found that IL-11 is an important target of TWF1 that regulates breast cancer cell invasion and STAT3 phosphorylation. The miR-30c-VIM/TWF1 signaling cascade is also associated with clinical outcome in breast cancer patients.
Original language | English (US) |
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Pages (from-to) | 373-382 |
Number of pages | 10 |
Journal | Breast Cancer Research and Treatment |
Volume | 137 |
Issue number | 2 |
DOIs | |
State | Published - Jan 2013 |
Funding
Funding This study was supported in part by The University of Chicago Women’s Board (J.B.), National Institutes of Health (NIH) T90 Regenerative Medicine Training Program DK070103-05, Department of Defense Breast Cancer Research Program W81XWH-09-1-0331, Paul Calabresi K12 Award 1K12CA139160-02, NCI K99 CA160638-01A1, Chicago Fellows Program at the University of Chicago, and the University of Chicago Clinical and Translational Science Award (UL1 RR024999) (H.L.), funds from the Sociedad Española de Oncología Médica (SEOM) (A.P.), the Breast SPORE at University of North Carolina 5-P50-CA58223-17 (A.P. and C.M.P.), the Breast SPORE at the University of Chicago P50CA125183-05, the Doris Duke Charitable Foundation (O.I.O and C.N.), The University of Chicago Cancer Research Center Pilot Fund, BSD Imaging Research Institute Pilot Research Projects Using Animal Imaging, UCMC/Northshore Collaborative Funds, a Carole and Gordon Segal Grant (G.L.G.), and the Virginia and D. K. Ludwig Fund (G.L.G. and H.L.), NIH Grants U54 CA 126524 and P01 CA139490 (M.F.C.), the Breast Cancer Research Foundation (M.F.C., O.I.O. and C.M.P), and the University of Chicago Cancer Center Support Grant CA 014599.
Keywords
- Breast tumor invasion
- IL-11
- TWF1
- VIM
- miR-30c
ASJC Scopus subject areas
- Oncology
- Cancer Research