title: ANGPTL2/LILRB2 signaling promotes the propagation of lung cancer cells.
abstract: Immune inhibitory receptors expressed on various types of immune cells deliver inhibitory signals that maintain the homeostasis of the immune system. Recently we demonstrated that leukocyte immunoglobulin-like receptor subfamily B member 2 (LILRB2) and its murine homolog, paired immunoglobulin-like receptor B (PIRB), are expressed on hematopoietic stem cells and acute myeloid leukemia stem cells and function in maintenance of stemness. Herein, we determined that both LILRB2 and its soluble ligand ANGPTL2 are highly expressed in non-small cell lung cancer (NSCLC) samples, and levels are adversely related to patient prognosis. Inhibition of LILRB2 expression in NSCLC cell lines, such as A549 cells, resulted in a dramatic decrease in proliferation, colony formation, and migration. Mechanistic analyses indicated that ANGPTL2 binds LILRB2 to support the growth of lung cancer cells and that the SHP2/CaMK1/CREB axis controls the proliferation of lung cancer cell lines. Our results suggest that signaling involving ANGPTL2 and LILRB2 is important for lung cancer development and represents a novel target for treatment of this type of cancer.
authors.affiliation: Institute of Health Sciences, Shanghai Institute for Biological Sciences, University of Chinese Academy of Science, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Hongqiao International Institute of Medicine, Shanghai Tongren Hospital, Faculty of Basic Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Xiaoye
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Pathology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Xiaoting
authors.initials: X
authors.lastname: Yu
authors.affiliation: Bingzhou Medical University, Taishan Scholar Program, Yantai, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Xie
authors.affiliation: Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Mengna
authors.initials: M
authors.lastname: Zhan
authors.affiliation: Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Li
authors.initials: L
authors.lastname: Xie
authors.affiliation: Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Hongxiang
authors.initials: H
authors.lastname: Zeng
authors.affiliation: Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Institute of Health Sciences, Shanghai Institute for Biological Sciences, University of Chinese Academy of Science, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of Pathology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Xianghua
authors.initials: X
authors.lastname: Yi
authors.affiliation: Hongqiao International Institute of Medicine, Shanghai Tongren Hospital, Faculty of Basic Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Junke
authors.initials: J
authors.lastname: Zheng
mesh_terms: D000091302:Angiopoietin-Like Protein 2; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins / Q000378:metabolism*; D054729:Calcium-Calmodulin-Dependent Protein Kinase Type 1 / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008024:Ligands; D008175:Lung Neoplasms / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009362:Neoplasm Metastasis; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C485792:ANGPTL2 protein, human; D000091302:Angiopoietin-Like Protein 2; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; C491341:LILRB2 protein, human; D008024:Ligands; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; C517596:CAMK1 protein, human; D054729:Calcium-Calmodulin-Dependent Protein Kinase Type 1; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11
keywords: ANGPTL2/LILRB2 signaling; CaMK1; lung cancer; metastasis