ANO9/TMEM16j promotes tumourigenesis via EGFR and is a novel therapeutic target for pancreatic cancer

Ikhyun Jun, Hyung Soon Park, He Piao, Jung Woo Han, Min Ji An, Byeong Gyu Yun, Xianglan Zhang, Yong Hoon Cha, You Keun Shin, Jong In Yook, Jinsei Jung, Heon Yung Gee, Joon Seong Park, Dong Sup Yoon, Hei Cheul Jeung, Min Goo Lee

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Abstract

Background: Anoctamin (ANO)/transmembrane member 16 (TMEM16) proteins mediate diverse physiological and pathophysiological functions including cancer cell proliferation. The present study aimed to identify the role of ANOs in pancreatic cancer. Methods: In an initial screen of ANOs, ANO9/TMEM16J was overexpressed in pancreatic cancer cells, and its role in the pathogenesis of pancreatic cancer was evaluated using an integrated in vitro and in vivo approach. To determine clinical relevance of the experimental findings, the prognostic value of ANO9 was evaluated in patients with pancreatic cancer. Results: The ANO9 mRNA and protein levels were increased in pancreatic cancer-derived cells. Exogenous expression of ANO9 in PANC-1 cells significantly increased cell proliferation in cell cultures and in mice. In contrast, knockdown of ANO9 in AsPC-1, BxPC-3, and Capan-2 cells strongly inhibited cell proliferation. Mechanistic analysis suggested that physical association of ANO9 with epidermal growth factor receptor (EGFR) underlies ANO9-induced cell proliferation. Knockdown of ANO9 augmented the effects of the EGFR inhibitor and the cytotoxic agent on pancreatic cancer cell proliferation. In addition, high ANO9 expression is a poor prognostic factor in patients with pancreatic cancer. Conclusions: The ANO9/TMEM16J appears to be a clinically useful prognostic marker for pancreatic cancer and a potential therapeutic target.

Original languageEnglish
Pages (from-to)1798-1809
Number of pages12
JournalBritish journal of cancer
Volume117
Issue number12
DOIs
Publication statusPublished - 2017 Jan 1

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All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Jun, I., Park, H. S., Piao, H., Han, J. W., An, M. J., Yun, B. G., Zhang, X., Cha, Y. H., Shin, Y. K., Yook, J. I., Jung, J., Gee, H. Y., Park, J. S., Yoon, D. S., Jeung, H. C., & Lee, M. G. (2017). ANO9/TMEM16j promotes tumourigenesis via EGFR and is a novel therapeutic target for pancreatic cancer. British journal of cancer, 117(12), 1798-1809. https://doi.org/10.1038/bjc.2017.355