Suppression of 14-3-3γ-mediated surface expression of ANO1 inhibits cancer progression of glioblastoma cells

Young Sun Lee, Jae Kwang Lee, Yeonju Bae, Bok Soon Lee, Eunju Kim, Chang Hoon Cho, Kanghyun Ryoo, Jiyun Yoo, Chul Ho Kim, Gwan Su Yi, Seok Geun Lee, C. Justin Lee, Sang Soo Kang, Eun Mi Hwang, Jae Yong Park

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16 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number26413
JournalScientific reports
Volume6
DOIs
Publication statusPublished - 2016 May 23

ASJC Scopus subject areas

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    Lee, Y. S., Lee, J. K., Bae, Y., Lee, B. S., Kim, E., Cho, C. H., Ryoo, K., Yoo, J., Kim, C. H., Yi, G. S., Lee, S. G., Lee, C. J., Kang, S. S., Hwang, E. M., & Park, J. Y. (2016). Suppression of 14-3-3γ-mediated surface expression of ANO1 inhibits cancer progression of glioblastoma cells. Scientific reports, 6, [26413]. https://doi.org/10.1038/srep26413