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Suppression of 14-3-3[gamma]-mediated surface expression of ANO1 inhibits cancer progression of glioblastoma cells

Anoctamin-1 (ANO1) acts as a Ca2+ -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...

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Published in:Scientific reports 2016-05, Vol.6, p.26413
Main Authors: Lee, Young-sun, Lee, Jae Kwang, Bae, Yeonju, Lee, Bok-soon, Kim, Eunju, Cho, Chang-hoon, Ryoo, Kanghyun, Yoo, Jiyun, Kim, Chul-ho, Yi, Gwan-su, Lee, Seok-geun, Lee, C Justin, Kang, Sang Soo, Hwang, Eun Mi, Park, Jae-yong
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container_title Scientific reports
container_volume 6
creator Lee, Young-sun
Lee, Jae Kwang
Bae, Yeonju
Lee, Bok-soon
Kim, Eunju
Cho, Chang-hoon
Ryoo, Kanghyun
Yoo, Jiyun
Kim, Chul-ho
Yi, Gwan-su
Lee, Seok-geun
Lee, C Justin
Kang, Sang Soo
Hwang, Eun Mi
Park, Jae-yong
description Anoctamin-1 (ANO1) acts as a Ca2+ -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.
doi_str_mv 10.1038/srep26413
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subjects 14-3-3 protein
Amino acids
Brain cancer
Calcium
Cancer
Chlorides
Gene silencing
Glioblastoma
Glioblastoma cells
Kinases
Localization
Medicine
Physiology
Plasma
Prostate
Proteins
Science
Tumors
Yeasts
title Suppression of 14-3-3[gamma]-mediated surface expression of ANO1 inhibits cancer progression of glioblastoma cells
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