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Nuclear SIPA1 activates integrin β1 promoter and promotes invasion of breast cancer cells

Oncogene volume 34, pages 1451–1462 (2015)Cite this article

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Abstract

SIPA1 (signal-induced proliferation-associated protein 1) is a GTPase activation protein that can catalyze the hydrolysis of Rap1 bound GTP to GDP. Recently attention has been paid to a potential role for SIPA1 in cancer metastasis; however, the underlying mechanism of how changes in SIPA1 levels may lead to increased metastasis remains poorly understood. In this study, we showed that SIPA1 was mainly localized to the nuclei in highly invasive breast cancer tumor tissue and MDA-MB-231 cells. Knockdown of SIPA1 in MDA-MB-231 altered cell morphology and cell proliferation ability. Furthermore, this study is the first to establish that nuclear SIPA1 can interact with the integrin β1 promoter and activate its transcription; this interaction appears to be important for SIPA1-dependent MDA-MB-231 cell adhesion and invasion. We also demonstrated that the phosphorylation of FAK, Akt and the expression of MMP9, downstream signaling molecules of integrin β1, were decreased upon SIPA1 knockdown, and MDA-MB-231 cell invasion was impaired. Taken together, these results suggest nuclear SIPA1 contributes to breast cancer cell invasion through the regulation of integrin β1 signaling.

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Acknowledgements

This work was supported partly by grants of National Basic Research Program of China (2011CB910401), NSFC (31271504) and 2009DFA31940 from The Ministry of Science and Technology, China.

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Author notes

  1. Y Zhang and Y Gong: These authors contributed equally to this work.

Authors and Affiliations

  1. Key Laboratory of Molecular Biophysics of Ministry of Education, School of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China

    Y Zhang, D Hu, P Zhu, N Wang, Q Zhang, A Aldeewan & L Su

  2. Department of Breast Surgery, Hubei Cancer Hospital, Wuhan, China

    Y Gong

  3. Department of Pathology, Hubei Cancer Hospital, Wuhan, China

    M Wang & H Xia

  4. Department of Thyroid and Breast Surgery, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

    X Qu

  5. Institute for Genomic and Personalized Medicine, School of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China

    B Z Ring

  6. Department of Immunology and Cell Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    N Minato

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Zhang, Y., Gong, Y., Hu, D. et al. Nuclear SIPA1 activates integrin β1 promoter and promotes invasion of breast cancer cells. Oncogene 34, 1451–1462 (2015). https://doi.org/10.1038/onc.2014.36

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