title: Loss of polarity protein AF6 promotes pancreatic cancer metastasis by inducing Snail expression.
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.
authors.affiliation: 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.
authors.forename: Yi
authors.initials: Y
authors.lastname: Xu
authors.affiliation: 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.
authors.forename: Renxu
authors.initials: R
authors.lastname: Chang
authors.affiliation: 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.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Peng
authors.affiliation: 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.
authors.forename: Yanmei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Ji
authors.affiliation: 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.
authors.forename: Jingyu
authors.initials: J
authors.lastname: Guo
authors.affiliation: 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.
authors.forename: Lele
authors.initials: L
authors.lastname: Song
authors.affiliation: 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.
authors.forename: Cheng
authors.initials: C
authors.lastname: Dai
authors.affiliation: 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.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.affiliation: 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.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Gastroenterology, Shanghai 2nd People's Hospital, Tongji University, School of Medicine, Shanghai 200011, China.
authors.forename: Xinjian
authors.initials: X
authors.lastname: Wan
authors.affiliation: Department of Pancreatic Surgery, Changhai Hospital, the Second Military Medical University, Shanghai 200433, China.
authors.forename: Chenghao
authors.initials: C
authors.lastname: Shao
authors.affiliation: 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.
authors.forename: Lixing
authors.initials: L
authors.lastname: Zhan
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D000072261:Dishevelled Proteins; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006801:Humans; D016547:Kinesins / Q000378:metabolism*; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009218:Myosins / Q000378:metabolism*; D009362:Neoplasm Metastasis; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: C095516:AFDN protein, human; D048868:Adaptor Proteins, Signal Transducing; C000606581:DVL2 protein, human; D000072261:Dishevelled Proteins; C000606582:Dvl2 protein, mouse; C106894:FOXE1 protein, human; D051858:Forkhead Transcription Factors; D010750:Phosphoproteins; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D009218:Myosins; D016547:Kinesins