ANO9/TMEM16J promotes tumourigenesis via EGFR and is a novel therapeutic target for pancreatic cancer

被引：43

作者：

Jun, Ikhyun ^{[1
,2
,3
]}

Park, Hyung Soon ^{[1
,2
,4
]}

Piao, He ^{[1
,2
]}

Han, Jung Woo ^{[1
,2
]}

An, Min Ji ^{[1
,2
]}

Yun, Byeong Gyu ^{[1
,2
]}

Zhang, Xianglan ^{[5
]}

Cha, Yong Hoon ^{[6
]}

Shin, You Keun ^{[7
,8
]}

Yook, Jong In ^{[6
]}

Jung, Jinsei ^{[9
]}

Gee, Heon Yung ^{[1
,2
]}

Park, Joon Seong ^{[10
]}

Yoon, Dong Sup ^{[10
]}

Jeung, Hei-Cheul ^{[7
,8
]}

Lee, Min Goo ^{[1
,2
]}

机构：

[1] Yonsei Univ, Coll Med, Dept Pharmacol, 50-1 Yonsei Ro, Seoul 03722, South Korea

[2] Yonsei Univ, Coll Med, Brain Korea PLUS Project Med Sci 21, 50-1 Yonsei Ro, Seoul 03722, South Korea

[3] Yonsei Univ, Coll Med, Dept Ophthalmol, Inst Vis Res, Seoul 03722, South Korea

[4] Yonsei Univ, Coll Med, Dept Internal Med, Div Med Oncol, Seoul 03722, South Korea

[5] Yonsei Univ, Coll Dent, Oral Canc Res Inst, Seoul 03722, South Korea

[6] Yonsei Univ, Coll Dent, Oral Canc Inst, Dept Oral Pathol, Seoul 03722, South Korea

[7] Yonsei Univ, Coll Med, Gangnam Severance Hosp, Div Med Oncol,Dept Internal Med, 211 Eonju Ro, Seoul 06273, South Korea

[8] Yonsei Univ, Coll Med, Songdang Inst Canc Res, Seoul 03722, South Korea

[9] Yonsei Univ, Coll Med, Dept Otorhinolaryngol, Seoul 03722, South Korea

[10] Yonsei Univ, Coll Med, Gangnam Severance Hosp, Dept Surg, Seoul 06273, South Korea

来源：

BRITISH JOURNAL OF CANCER | 2017年 / 117卷 / 12期

基金：

新加坡国家研究基金会;

关键词：

pancreatic cancer; ANO9/TMEM16J; EGFR; cell proliferation; target; prognostic factor; EXPRESSION; TMEM16A; RECEPTOR; ANO1; GENE; KRAS; IDENTIFICATION; PERMEABILITY; PROGRESSION; MUTATIONS;

D O I：

10.1038/bjc.2017.355

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：1798 / 1809

页数：12

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