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ANO9/TMEM16J通过表皮生长因子受体促进肿瘤发生，是胰腺癌的一个新的治疗靶点。

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

作者信息

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

机构信息

Department of Pharmacology and Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine, 50-1, Yonsei-Ro, Seodaemun-Gu, Seoul 03722, Korea.

The Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine 03722, Seoul, Korea.

出版信息

Br J Cancer. 2017 Dec 5;117(12):1798-1809. doi: 10.1038/bjc.2017.355. Epub 2017 Oct 12.

DOI:10.1038/bjc.2017.355
PMID:29024940
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5729472/
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.

摘要

背景

anoctamin（ANO）/跨膜蛋白16（TMEM16）家族蛋白介导多种生理和病理生理功能，包括癌细胞增殖。本研究旨在确定ANO在胰腺癌中的作用。

方法

在对ANO的初步筛选中，ANO9/TMEM16J在胰腺癌细胞中过表达，并采用体外和体内相结合的方法评估其在胰腺癌发病机制中的作用。为了确定实验结果的临床相关性，评估了ANO9在胰腺癌患者中的预后价值。

结果

胰腺癌来源的细胞中ANO9的mRNA和蛋白水平升高。在PANC-1细胞中外源性表达ANO9显著增加了细胞培养物和小鼠中的细胞增殖。相反，在AsPC-1、BxPC-3和Capan-2细胞中敲低ANO9强烈抑制细胞增殖。机制分析表明，ANO9与表皮生长因子受体（EGFR）的物理结合是ANO9诱导细胞增殖的基础。敲低ANO9增强了EGFR抑制剂和细胞毒性药物对胰腺癌细胞增殖的作用。此外，ANO9高表达是胰腺癌患者的不良预后因素。

结论

ANO9/TMEM16J似乎是一种对胰腺癌具有临床实用价值的预后标志物和潜在的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4255/5729472/e61be20ef858/bjc2017355f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4255/5729472/d39c5ccf80ec/bjc2017355f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4255/5729472/f9708ca92517/bjc2017355f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4255/5729472/2e6e027246a0/bjc2017355f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4255/5729472/dcd87a938b3d/bjc2017355f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4255/5729472/52946cd42790/bjc2017355f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4255/5729472/e61be20ef858/bjc2017355f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4255/5729472/d39c5ccf80ec/bjc2017355f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4255/5729472/f9708ca92517/bjc2017355f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4255/5729472/2e6e027246a0/bjc2017355f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4255/5729472/dcd87a938b3d/bjc2017355f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4255/5729472/52946cd42790/bjc2017355f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4255/5729472/e61be20ef858/bjc2017355f6.jpg

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