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FYN promotes mesenchymal phenotypes of basal type breast cancer cells through STAT5/NOTCH2 signaling node

Oncogene volume 37, pages 1857–1868 (2018)Cite this article

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Abstract

Basal type breast cancer is the most aggressive and has mesenchymal features with a high metastatic ability. However, the signaling node that determines the basal type features in breast cancer remains obscure. Here, we report that FYN among SRC family kinases is required for the maintenance of basal type breast cancer subtype. Importantly, FYN enhanced NOTCH2 activation in basal type breast cancer cells through STAT5-mediated upregulation of Jagged-1 and DLL4 NOTCH ligands, thereby contributed to mesenchymal phenotypes. In addition, we found that high levels of FYN persist in basal type breast cancer cells by a positive feedback loop between FYN and STAT5. FYN interacted directly with STAT5 and increased p-STAT5 that further acts as a transcription factor for FYN. Taken together, our findings demonstrate a pivotal role of FYN and its downstream effectors in maintaining the basal type features in breast cancer.

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Acknowledgements

This work was supported by the National Research Foundation (NRF) and Ministry of Science, ICT and Future Planning, Korean Government, through its National Nuclear Technology Program (NRF-2016R1E1A1A01942075 and NRF-2017M2A2A7070460).

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  1. Ga-Hang Lee and Ki-Chun Yoo contributed equally to this work.

Authors and Affiliations

  1. Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul, Korea

    Ga-Hang Lee, Ki-Chun Yoo, Yoojeong An, Nizam Uddin, Yongjoon Suh & Su-Jae Lee

  2. Department of Radiation Oncology, Samsung Medical Center, Seoul, Korea

    Ga-Hang Lee

  3. Division of Radiation Effect, Korea Institute of Radiological and Medical Sciences, Seoul, Korea

    Hae-June Lee & Minyoung Lee

  4. Centre of Excellence in Molecular Biology (CEMB), University of the Punjab, Lahore, Pakistan

    Nizam Uddin

  5. Laboratory of Radiation Exposure & Therapeutics, National Radiation Emergency Medical Center, Korea Institute of Radiological and Medical Sciences, Seoul, Korea

    Min-Jung Kim

  6. Department of Radiation Biology, Environmental Radiation Research Group, Korea Atomic Energy Research Institute, Daejeon, Republic of Korea

    In-Gyu Kim

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  1. Ga-Hang Lee
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Correspondence to Yongjoon Suh or Su-Jae Lee.

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Lee, GH., Yoo, KC., An, Y. et al. FYN promotes mesenchymal phenotypes of basal type breast cancer cells through STAT5/NOTCH2 signaling node. Oncogene 37, 1857–1868 (2018). https://doi.org/10.1038/s41388-017-0114-y

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