title: Suppression of 14-3-3γ-mediated surface expression of ANO1 inhibits cancer progression of glioblastoma cells.
abstract: Anoctamin-1 (ANO1) acts as a Ca(2+)-activated Cl(-) channel in various normal tissues, and its expression is increased in several different types of cancer. Therefore, understanding the regulation of ANO1 surface expression is important for determining its physiological and pathophysiological functions. However, the trafficking mechanism of ANO1 remains elusive. Here, we report that segment a (N-terminal 116 amino acids) of ANO1 is crucial for its surface expression, and we identified 14-3-3γ as a binding partner for anterograde trafficking using yeast two-hybrid screening. The surface expression of ANO1 was enhanced by 14-3-3γ, and the Thr9 residue of ANO1 was critical for its interaction with 14-3-3γ. Gene silencing of 14-3-3γ and/or ANO1 demonstrated that suppression of ANO1 surface expression inhibited migration and invasion of glioblastoma cells. These findings provide novel therapeutic implications for glioblastomas, which are associated with poor prognosis.
authors.affiliation: School of Biosystem and Biomedical Science, College of Health Science, Korea University, Seoul 02841, Republic of Korea.|Department of Anatomy and Convergence Medical Science, Institute of Health Sciences, School of Medicine, Gyeongsang National University, Jinju 52727, Republic of Korea.|Center for Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea.
authors.forename: Young-Sun
authors.initials: YS
authors.lastname: Lee
authors.affiliation: Neuroscience Program, University of Science and Technology (UST), Daejeon 34113, Republic of Korea.
authors.forename: Jae Kwang
authors.initials: JK
authors.lastname: Lee
authors.affiliation: School of Biosystem and Biomedical Science, College of Health Science, Korea University, Seoul 02841, Republic of Korea.
authors.forename: Yeonju
authors.initials: Y
authors.lastname: Bae
authors.affiliation: Department of Otolaryngology, Ajou University School of Medicine, Suwon 16499, Republic of Korea.
authors.forename: Bok-Soon
authors.initials: BS
authors.lastname: Lee
authors.affiliation: School of Biosystem and Biomedical Science, College of Health Science, Korea University, Seoul 02841, Republic of Korea.|Center for Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea.
authors.forename: Eunju
authors.initials: E
authors.lastname: Kim
authors.affiliation: School of Biosystem and Biomedical Science, College of Health Science, Korea University, Seoul 02841, Republic of Korea.
authors.forename: Chang-Hoon
authors.initials: CH
authors.lastname: Cho
authors.affiliation: School of Biosystem and Biomedical Science, College of Health Science, Korea University, Seoul 02841, Republic of Korea.
authors.forename: Kanghyun
authors.initials: K
authors.lastname: Ryoo
authors.affiliation: Division of Applied Life Science (BK21 plus), Research Institute of Life Sciences, Gyeongsang National University, Jinju 52828, Korea.
authors.forename: Jiyun
authors.initials: J
authors.lastname: Yoo
authors.affiliation: Department of Otolaryngology, Ajou University School of Medicine, Suwon 16499, Republic of Korea.
authors.forename: Chul-Ho
authors.initials: CH
authors.lastname: Kim
authors.affiliation: Department of Bio and Brain Engineering, KAIST, Daejeon 34141, Republic of Korea.
authors.forename: Gwan-Su
authors.initials: GS
authors.lastname: Yi
authors.affiliation: Department of Science in Korean Medicine, College of Korean Medicine, KHU-KIST department of Convergging Science and Technology, Kyung Hee University, Seoul 02447, Republic of Korea.
authors.forename: Seok-Geun
authors.initials: SG
authors.lastname: Lee
authors.affiliation: Center for Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea.|Neuroscience Program, University of Science and Technology (UST), Daejeon 34113, Republic of Korea.
authors.forename: C Justin
authors.initials: CJ
authors.lastname: Lee
authors.affiliation: Department of Anatomy and Convergence Medical Science, Institute of Health Sciences, School of Medicine, Gyeongsang National University, Jinju 52727, Republic of Korea.
authors.forename: Sang Soo
authors.initials: SS
authors.lastname: Kang
authors.affiliation: Center for Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea.|Neuroscience Program, University of Science and Technology (UST), Daejeon 34113, Republic of Korea.
authors.forename: Eun Mi
authors.initials: EM
authors.lastname: Hwang
authors.affiliation: School of Biosystem and Biomedical Science, College of Health Science, Korea University, Seoul 02841, Republic of Korea.
authors.forename: Jae-Yong
authors.initials: JY
authors.lastname: Park
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism*; D000075369:Anoctamin-1 / Q000737:chemistry* / Q000378:metabolism*; D001665:Binding Sites; D001932:Brain Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D020798:Two-Hybrid System Techniques
chemical_list: D048948:14-3-3 Proteins; C476213:ANO1 protein, human; D000075369:Anoctamin-1; D009363:Neoplasm Proteins; C000610447:YWHAG protein, human