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Angiomotin-like 2 interacts with and negatively regulates AKT

Oncogene volume 36, pages 4662–4669 (2017)Cite this article

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Abstract

Angiomotin-like 2 (AMOTL2) is a member of Angiomotin family proteins, which are potent inhibitors for the Hippo pathway effector YAP. However, additional cellular functions of AMOTL2 besides YAP inhibition are largely unknown. Here, we reported that AMOTL2 associates with and negatively regulates AKT. Mechanistically, AMOTL2 binds to AKT pleckstrin homology domain and interrupts AKT’s membrane localization. Liver-specific depletion of AMOTL2 enlarged mouse liver and activated both YAP and AKT. Downregulation of AMOTL2 is found in human liver cancers, correlating with the concomitant activation of YAP and AKT. Together, our results provide novel insights into a dual tumor suppressive function of AMOTL2 by targeting both YAP and AKT in liver size control and cancer prevention.

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Acknowledgements

WW thanks Dr Junjie Chen at MD Anderson Cancer Center for his mentoring and continuous support. We also thank Kathryn E Aziz and My Kim Tran at MD Anderson Cancer Center for the technical help. WW is a recipient of American Association for Cancer Research Career Development Award for Translational Breast Cancer Research supported by the Breast Cancer Research Foundation (16-20-26-WANG). This work was also partially supported by the American Cancer Society-Institutional Research Grant to WW. WW is a member of Chao Family Comprehensive Cancer Center (P30 CA062203) and a member of Center for Complex Biological Systems at UC Irvine.

Author contributions

WW conceived the experiments and wrote the manuscript. HH, BY and WW performed all of the experiments.

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  1. Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA, USA

    H Han, B Yang & W Wang

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Correspondence to W Wang.

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Han, H., Yang, B. & Wang, W. Angiomotin-like 2 interacts with and negatively regulates AKT. Oncogene 36, 4662–4669 (2017). https://doi.org/10.1038/onc.2017.101

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