title: IL-33 signaling fuels outgrowth and metastasis of human lung cancer.
abstract: IL-33 is a member of IL-1 superfamily that drives production of Th2-related cytokines. Recently, accumulating evidence suggest an involvement of IL-33 in carcinogenesis. Herein, we determine a close correlation of IL-33 expression and cancer progress in patients with non-small-cell lung cancer (NSCLC). Overexpression of IL-33 by transfection with IL-33 expression vector enhances NSCLC outgrowth and metastasis, while genetic knockdown of IL-33 by transfection with IL-33 shRNA limits NSCLC progression. In consistent, IL-33 stimulation of NSCLC cells leads to robust NSCLC outgrowth and metastasis in vitro and in vivo. Mechanically, IL-33-triggered NSCLC progression relies on ST2 receptor and could be abrogated by ST2 blockade. IL-33/ST2 pathway up-regulates membrane glucose transporter 1 (GLUT1) on NSCLC cells, enhancing their glucose uptake and glycolysis. Accordingly, interfering GLUT1 expression dampens IL-33-enhanced glucose uptake and glycolysis in NSCLC cells, thereby abrogates IL-33-induced NSCLC outgrowth and metastasis. In essence, these findings derived from patients' NSCLC cells uncover a new function of IL-33 in NSCLC pathogenesis and identify GLUT1 as a novel target of IL-33 signaling. Block IL-33 is a promising therapeutic strategy to limit NSCLC glycolysis and tumor progression in clinical practice.
authors.affiliation: Department of Microbiology, School of Medicine, Qingdao University, Qingdao 266071, China; Department of Respiratory Medicine, East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
authors.forename: Chunhong
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Clinical Laboratory, Qingdao Municipal Hospital, Qingdao 266071, China.
authors.forename: Zengsheng
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Clinical Laboratory, Qingdao Women & Children Hospital, Qingdao 266034, China.
authors.forename: Xiangmao
authors.initials: X
authors.lastname: Bu
authors.affiliation: Department of Pathology, East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Han
authors.affiliation: Department of Respiratory Medicine, East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Shan
authors.affiliation: Department of Respiratory Medicine, East Hospital, Tongji University School of Medicine, Shanghai 200120, China. Electronic address: rentaosh@126.com.
authors.forename: Tao
authors.initials: T
authors.lastname: Ren
authors.affiliation: Department of Microbiology, School of Medicine, Qingdao University, Qingdao 266071, China; Department of Clinical Laboratory, Qingdao Municipal Hospital, Qingdao 266071, China. Electronic address: wqsongqd@126.com.
authors.forename: Weiqing
authors.initials: W
authors.lastname: Song
mesh_terms: D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism*; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D005947:Glucose / Q000737:chemistry; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D006019:Glycolysis; D006801:Humans; D000072179:Interleukin-1 Receptor-Like 1 Protein / Q000378:metabolism; D000067596:Interleukin-33 / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D015398:Signal Transduction
chemical_list: D051272:Glucose Transporter Type 1; C079241:IL1RL1 protein, human; C506536:IL33 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; C495677:SLC2A1 protein, human; D005947:Glucose
keywords: GLUT1; IL-33; Lung cancer