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Angiomotin decreases lung cancer progression by sequestering oncogenic YAP/TAZ and decreasing Cyr61 expression

Oncogene volume 34, pages 4056–4068 (2015)Cite this article

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Abstract

Lung cancer is the leading cause of cancer death worldwide, with metastasis underlying majority of related deaths. Angiomotin (AMOT), a scaffold protein, has been shown to interact with oncogenic Yes-associated protein/transcriptional co-activator with a PDZ-binding motif (YAP/TAZ) proteins, suggesting a potential role in tumor progression. However, the functional role of AMOT in lung cancer remains unknown. This study aimed to identify the patho-physiological characteristics of AMOT in lung cancer progression. Results revealed that AMOT expression was significantly decreased in clinical lung cancer specimens. Knockdown of AMOT in a low metastatic CL1-0 lung cancer cell line initiated cancer proliferation, migration, invasion and epithelial–mesenchymal transition. The trigger of cancer progression caused by AMOT loss was transduced by decreased cytoplasmic sequestration and increased nuclear translocation of oncogenic co-activators YAP/TAZ, leading to increased expression of the growth factor, Cyr61. Tumor promotion by AMOT knockdown was reversed when YAP/TAZ or Cyr61 was absent. Further, AMOT knockdown increased the growth and spread of Lewis lung carcinoma in vivo. These findings suggest that AMOT is a crucial suppressor of lung cancer metastasis and highlight its critical role as a tumor suppressor and its potential as a prognostic biomarker and therapeutic target for lung cancer.

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Acknowledgements

This study was supported by grants from the National Science Council of Taiwan (NSC 101-2628-B-037-001-MY3; NSC 101-2320-B-037-043-MY3), the Ministry of Science and Technology (MOST 103-2320-B-037-006-MY3; MOST 103-2314-B-037-052), the Kaohsiung Medical University “Aim for the top 500 universities grant, Grant No. KMU-DT103008”, the Research Center for Environmental Medicine, Kaohsiung Medical University (KMU-TP103A19; KMU-TP103A20) and the Kaohsiung Medical University Hospital Research Foundation (KMUH102-2T06). We also thank the Center for Resources, Research, and Development of Kaohsiung Medical University for their support with the instrumentation.

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Authors and Affiliations

  1. Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Y-L Hsu & M-J Tsai

  2. Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

    J-Y Hung, M-S Huang, M-J Tsai, Y-S Lin & C-Y Wu

  3. School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    J-Y Hung & M-S Huang

  4. Division of Chest Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

    S-H Chou

  5. Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    S-Y Chiang, Y-W Ho & P-L Kuo

  6. Research Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    P-L Kuo

  7. Institute of Medical Science and Technology, National Sun Yat-Sen University, Kaohsiung, Taiwan

    P-L Kuo

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Hsu, YL., Hung, JY., Chou, SH. et al. Angiomotin decreases lung cancer progression by sequestering oncogenic YAP/TAZ and decreasing Cyr61 expression. Oncogene 34, 4056–4068 (2015). https://doi.org/10.1038/onc.2014.333

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