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

Research output: Contribution to journalArticle

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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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Pancreatic Neoplasms
Epidermal Growth Factor Receptor
Cell Proliferation
Therapeutics
Cytotoxins
Proteins
Cell Culture Techniques
Messenger RNA
Neoplasms

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., ... 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
Jun, Ikhyun ; Park, Hyung Soon ; Piao, He ; Han, Jung Woo ; An, Min Ji ; Yun, Byeong Gyu ; Zhang, Xianglan ; Cha, Yong Hoon ; Shin, You Keun ; Yook, Jong In ; Jung, Jinsei ; Gee, Heon Yung ; Park, Joon Seong ; Yoon, Dong Sup ; Jeung, Hei Cheul ; Lee, Min Goo. / ANO9/TMEM16j promotes tumourigenesis via EGFR and is a novel therapeutic target for pancreatic cancer. In: British journal of cancer. 2017 ; Vol. 117, No. 12. pp. 1798-1809.
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title = "ANO9/TMEM16j promotes tumourigenesis via EGFR and is a novel therapeutic target for pancreatic cancer",
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.",
author = "Ikhyun Jun and Park, {Hyung Soon} and He Piao and Han, {Jung Woo} and An, {Min Ji} and Yun, {Byeong Gyu} and Xianglan Zhang and Cha, {Yong Hoon} and Shin, {You Keun} and Yook, {Jong In} and Jinsei Jung and Gee, {Heon Yung} and Park, {Joon Seong} and Yoon, {Dong Sup} and Jeung, {Hei Cheul} and Lee, {Min Goo}",
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Jun, I, Park, HS, Piao, H, Han, JW, An, MJ, Yun, BG, Zhang, X, Cha, YH, Shin, YK, Yook, JI, Jung, J, Gee, HY, Park, JS, Yoon, DS, Jeung, HC & Lee, MG 2017, 'ANO9/TMEM16j promotes tumourigenesis via EGFR and is a novel therapeutic target for pancreatic cancer', British journal of cancer, vol. 117, no. 12, pp. 1798-1809. https://doi.org/10.1038/bjc.2017.355

ANO9/TMEM16j promotes tumourigenesis via EGFR and is a novel therapeutic target for pancreatic cancer. / Jun, Ikhyun; Park, Hyung Soon; Piao, He; Han, Jung Woo; An, Min Ji; Yun, Byeong Gyu; Zhang, Xianglan; Cha, Yong Hoon; Shin, You Keun; Yook, Jong In; Jung, Jinsei; Gee, Heon Yung; Park, Joon Seong; Yoon, Dong Sup; Jeung, Hei Cheul; Lee, Min Goo.

In: British journal of cancer, Vol. 117, No. 12, 01.01.2017, p. 1798-1809.

Research output: Contribution to journalArticle

TY - JOUR

T1 - ANO9/TMEM16j promotes tumourigenesis via EGFR and is a novel therapeutic target for pancreatic cancer

AU - Jun, Ikhyun

AU - Park, Hyung Soon

AU - Piao, He

AU - Han, Jung Woo

AU - An, Min Ji

AU - Yun, Byeong Gyu

AU - Zhang, Xianglan

AU - Cha, Yong Hoon

AU - Shin, You Keun

AU - Yook, Jong In

AU - Jung, Jinsei

AU - Gee, Heon Yung

AU - Park, Joon Seong

AU - Yoon, Dong Sup

AU - Jeung, Hei Cheul

AU - Lee, Min Goo

PY - 2017/1/1

Y1 - 2017/1/1

N2 - 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.

AB - 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.

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