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Nat Commun. 2015 May 26;6:7184. doi: 10.1038/ncomms8184.

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

Author information

1
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.
2
1] Department of Pancreatic Surgery, Changhai Hospital, the Second Military Medical University, Shanghai 200433, China [2] Navy Medical Research Institute, the Second Military Medical University, Shanghai 200433, China.
3
Department of Gastroenterology, Shanghai 2nd People's Hospital, Tongji University, School of Medicine, Shanghai 200011, China.
4
Department of Pancreatic Surgery, Changhai Hospital, the Second Military Medical University, Shanghai 200433, China.
5
1] 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 [2] Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing 100021, China.

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.

PMID:
26013125
DOI:
10.1038/ncomms8184
[Indexed for MEDLINE]

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