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

Yi Xu, Renxu Chang, Zhiyong Peng, Yanmei Wang, Weiwei Ji, Jingyu Guo, Lele Song, Cheng Dai, Wei Wei, Yanjun Wu, Xinjian Wan, Chenghao Shao and Lixing Zhan ()
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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
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

Nature Communications, 2015, vol. 6, issue 1, 1-12

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms8184

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