医学
癌症研究
转移
癌症
肺癌
免疫疗法
原发性肿瘤
肿瘤科
内科学
作者
Xiaohu Zheng,Min Cheng,Binqing Fu,Xiaolei Fan,Qing Wang,Xiaoqing Yu,Rui Sun,Zhigang Tian,Haiming Wei
出处
期刊:Cancer Research
[American Association for Cancer Research]
日期:2015-01-20
卷期号:75 (6): 1080-1090
被引量:25
标识
DOI:10.1158/0008-5472.can-14-1831
摘要
Abstract There remains a great need for effective therapies for lung cancer, the majority of which are non–small cell lung cancers (NSCLC). Here, we report the identification of a novel candidate therapeutic target, LUNX, as a molecule overexpressed in primary NSCLC and lymph node metastases that is associated with reduced postoperative survival. Functional studies demonstrated that LUNX overexpression promoted lung cancer cell migration and proliferation by interactions with the chaperone protein 14-3-3. Conversely, LUNX silencing disrupted primary tumor growth, local invasion, and metastatic colonization. The finding that LUNX was expressed on cell membranes prompted us to generate and characterize LUNX antibodies as a candidate therapeutic. Anti-LUNX could downregulate LUNX and reduce lung cancer cell proliferation and migration in vitro. Administered in vivo to mice bearing lung cancer xenografts, anti-LUNX could slow tumor growth and metastasis and improve mouse survival. Together, our work provides a preclinical proof of concept for LUNX as a novel candidate target for immunotherapy in lung cancer. Cancer Res; 75(6); 1080–90. ©2015 AACR.
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