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

Authors
 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 
Citation
 British Journal of Cancer, Vol.117(12) : 1798-1809, 2017 
Journal Title
 British Journal of Cancer 
ISSN
 0007-0920 
Issue Date
2017
MeSH
Adult ; Aged ; Aged, 80 and over ; Animals ; Anoctamins/genetics* ; Anoctamins/metabolism* ; Anti-Bacterial Agents/therapeutic use ; Antineoplastic Agents/pharmacology ; Biomarkers, Tumor/genetics ; Biomarkers, Tumor/metabolism ; Carcinogenesis ; Carcinoma, Pancreatic Ductal/drug therapy ; Carcinoma, Pancreatic Ductal/genetics* ; Carcinoma, Pancreatic Ductal/metabolism* ; Cell Line, Tumor ; Cell Proliferation/genetics ; Deoxycytidine/analogs & derivatives ; Deoxycytidine/pharmacology ; Disease-Free Survival ; Doxycycline/therapeutic use ; Erlotinib Hydrochloride/pharmacology ; Female ; Gene Knockdown Techniques ; HEK293 Cells ; Humans ; Male ; Membrane Proteins/genetics ; Membrane Proteins/metabolism* ; Mice ; Middle Aged ; Neoplasm Transplantation ; Pancreatic Neoplasms/drug therapy ; Pancreatic Neoplasms/genetics* ; Pancreatic Neoplasms/metabolism* ; Phospholipid Transfer Proteins/genetics* ; Phospholipid Transfer Proteins/metabolism* ; Prognosis ; RNA, Messenger/metabolism ; Receptor, Epidermal Growth Factor/antagonists & inhibitors ; Receptor, Epidermal Growth Factor/metabolism* ; Survival Rate ; Tumor Stem Cell Assay
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.
Full Text
http://www.nature.com/articles/bjc2017355
DOI
10.1038/bjc.2017.355
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Ophthalmology (안과학교실)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Otorhinolaryngology (이비인후과학교실)
Yonsei Authors
박학(Piao He) ORCID logo https://orcid.org/0000-0002-1817-3167
박형순(Park, Hyung Soon)
이민구(Lee, Min Goo) ORCID logo https://orcid.org/0000-0001-7436-012X
전익현(Jun, Ik Hyun) ORCID logo https://orcid.org/0000-0002-2160-1679
정진세(Jung, Jinsei) ORCID logo https://orcid.org/0000-0003-1906-6969
정희철(Jeung, Hei Cheul)
지헌영(Gee, Heon Yung) ORCID logo https://orcid.org/0000-0002-8741-6177
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/161631
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