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MicroRNA-30c targets cytoskeleton genes involved in breast cancer cell invasion

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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.

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Acknowledgments

We are very thankful to Dr. Jun Lu at Yale University for providing the miR-30c precursor gene vector, Dr. Seo Young Park for data analyses, and Dr. John Kokontis for helping review and edit our manuscript. We appreciate the experimental support of several core facilities, including the Animal Facility, Optical Imaging Core Facility, Flow Cytometry Facility, Integrated Microscopy Core Facility, DNA Sequencing Facility, Functional Genomics Facility, and IHC Core Facility at the University of Chicago. We specifically acknowledge Ryan Duggan, James Cao, David Leclerc, Marianne Greene, Terri Li, Xin Jiang, Shirley Bond, Jaejung Kim, Hui Zheng, Andrew Gusev, Dalong Qian, and Yohei Shimono for technical help and support.

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.

Conflicts of interest

Authors of this manuscript have no conflict of interest.

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Author notes

  1. Aleix Prat

    Present address: Translational Genomics Group, Vall D′Hebron Institute of Oncology (VHIO), Barcelona, 08035, Spain

Authors and Affiliations

  1. The Ben May Department for Cancer Research, The University of Chicago, Chicago, IL, 60637, USA

    Jessica Bockhorn, Kathy Yee, Ya-Fang Chang, Rachel Dalton, Simo Huang, Kaitlin E. Swanson, Geoffrey L. Greene & Huiping Liu

  2. Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL, 60637, USA

    Jessica Bockhorn

  3. Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA

    Aleix Prat & Charles M. Perou

  4. Department of Health Studies, The University of Chicago, Chicago, IL, 60637, USA

    Dezheng Huo

  5. Center for Clinical Cancer Genetics, Department of Medicine, The University of Chicago, Chicago, IL, 60637, USA

    Chika Nwachukwu & Olufunmilayo I. Olopade

  6. The Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA, 94305, USA

    Michael F. Clarke & Huiping Liu

Authors
  1. Jessica Bockhorn
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Corresponding authors

Correspondence to Geoffrey L. Greene or Huiping Liu.

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Bockhorn, J., Yee, K., Chang, YF. et al. MicroRNA-30c targets cytoskeleton genes involved in breast cancer cell invasion. Breast Cancer Res Treat 137, 373–382 (2013). https://doi.org/10.1007/s10549-012-2346-4

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  • DOI: https://doi.org/10.1007/s10549-012-2346-4

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