title: Targeting LUNX inhibits non-small cell lung cancer growth and metastasis.
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.
authors.affiliation: 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.
authors.forename: Xiaohu
authors.initials: X
authors.lastname: Zheng
authors.affiliation: 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.
authors.forename: Min
authors.initials: M
authors.lastname: Cheng
authors.affiliation: 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.
authors.forename: Binqing
authors.initials: B
authors.lastname: Fu
authors.affiliation: 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.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Fan
authors.affiliation: Anhui Chest Hospital, Hefei, Anhui, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
authors.affiliation: The First People's Hospital of Hefei, Hefei, Anhui, China.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Yu
authors.affiliation: 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.
authors.forename: Rui
authors.initials: R
authors.lastname: Sun
authors.affiliation: 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.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Tian
authors.affiliation: 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.
authors.forename: Haiming
authors.initials: H
authors.lastname: Wei
mesh_terms: D048948:14-3-3 Proteins / Q000502:physiology; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D006023:Glycoproteins / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009361:Neoplasm Invasiveness; D010750:Phosphoproteins / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D048948:14-3-3 Proteins; C485599:BPIFA1 protein, human; D006023:Glycoproteins; D010750:Phosphoproteins; C482984:YWHAH protein, human