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Loss of polarity protein AF6 promotes pancreatic cancer metastasis by inducing Snail expression

Author

Listed:
  • Yi Xu

    (Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, 294 Taiyuan Road, Shanghaim 200031, China)

  • Renxu Chang

    (Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, 294 Taiyuan Road, Shanghaim 200031, China)

  • Zhiyong Peng

    (Changhai Hospital, the Second Military Medical University
    Navy Medical Research Institute, the Second Military Medical University)

  • Yanmei Wang

    (Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, 294 Taiyuan Road, Shanghaim 200031, China)

  • Weiwei Ji

    (Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, 294 Taiyuan Road, Shanghaim 200031, China)

  • Jingyu Guo

    (Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, 294 Taiyuan Road, Shanghaim 200031, China)

  • Lele Song

    (Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, 294 Taiyuan Road, Shanghaim 200031, China)

  • Cheng Dai

    (Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, 294 Taiyuan Road, Shanghaim 200031, China)

  • Wei Wei

    (Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, 294 Taiyuan Road, Shanghaim 200031, China)

  • Yanjun Wu

    (Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, 294 Taiyuan Road, Shanghaim 200031, China)

  • Xinjian Wan

    (Shanghai 2nd People’s Hospital, Tongji University, School of Medicine)

  • Chenghao Shao

    (Changhai Hospital, the Second Military Medical University)

  • Lixing Zhan

    (Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, 294 Taiyuan Road, Shanghaim 200031, China
    Key Laboratory of Food Safety Risk Assessment, Ministry of Health)

Abstract

Pancreatic cancer (PC) is a particularly lethal form of cancer with high potential for metastasis to distant organs. Disruption of cell polarity is a hallmark of advanced epithelial tumours. Here we show that the polarity protein AF6 (afadin and MLLT4) is expressed at low levels in PC. We demonstrate that depletion of AF6 markedly promotes proliferation and metastasis of PC cells through upregulation of the expression of Snail protein, and this requires the nuclear localization of AF6. Furthermore, AF6 deficiency in PC cells leads to increased formation of a Dishevelled 2 (Dvl2)–FOXE1 complex on the promoter region of Snail gene, and activation of Snail expression. Altogether, our data established AF6 as a potential inhibitor of metastasis in PC cells. Targeting the Dvl2–FOXE1–Snail signalling axis may thus represent a promising therapeutic strategy.

Suggested Citation

  • Yi Xu & Renxu Chang & Zhiyong Peng & Yanmei Wang & Weiwei Ji & Jingyu Guo & Lele Song & Cheng Dai & Wei Wei & Yanjun Wu & Xinjian Wan & Chenghao Shao & Lixing Zhan, 2015. "Loss of polarity protein AF6 promotes pancreatic cancer metastasis by inducing Snail expression," Nature Communications, Nature, vol. 6(1), pages 1-12, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8184
    DOI: 10.1038/ncomms8184
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    Cited by:

    1. Marilyn Goudreault & Valérie Gagné & Chang Hwa Jo & Swati Singh & Ryan C. Killoran & Anne-Claude Gingras & Matthew J. Smith, 2022. "Afadin couples RAS GTPases to the polarity rheostat Scribble," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

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