Targeting LUNX inhibits non-small cell lung cancer growth and metastasis

Xiaohu Zheng  ¹ , Min Cheng  ² , Binqing Fu  ¹ , Xiaolei Fan  ¹ , Qing Wang  ³ , Xiaoqing Yu  ⁴ , Rui Sun  ¹ , Zhigang Tian  ⁵ , Haiming Wei  ⁵

Affiliations

• ¹ Institute of Immunology, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, China. Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China, Hefei, Anhui, China.
• ² Institute of Immunology, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, China. Anhui Province Hospital Affiliated Anhui Medical University, Hefei, Anhui, China.
• ³ Anhui Chest Hospital, Hefei, Anhui, China.
• ⁴ The First People’s Hospital of Hefei, Hefei, Anhui, China.
• ⁵ Institute of Immunology, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, China. Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China, Hefei, Anhui, China. ustcwhm@ustc.edu.cn tzg@ustc.edu.cn.

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.