title: TIPE2 suppresses angiogenesis and non-small cell lung cancer (NSCLC) invasiveness via inhibiting Rac1 activation and VEGF expression.
abstract: Non-small cell lung cancer (NSCLC) is one of the leading causes of all cancer-related deaths worldwide. Despite extensive efforts to improve the diagnosis and treatment of this neoplasm, limited progress has been made. Tumor necrosis factor (TNF)-alpha-induced protein 8-like 2 (TIPE2 or TNFAIP8L2) is a newly introduced negative immune regulator, which also controls tumorigenesis. However, the role of TIPE2 in angiogenesis is unknown. In the present study, we investigated the expression and roles of TIPE2 in NSCLC. TIPE2 upregulation in human NSCLC tissues was negatively associated with the primary tumor size, lymph node metastasis, and advanced clinical stage, which can be used to predict lymph node metastasis. Moreover, overexpression of TIPE2 not only inhibited the colony formation, migration, and invasion of NSCLC cells but also indirectly suppressed the proliferation, migration, and tube formation of vascular endothelial cells. Furthermore, TIPE2 suppressed tumor invasiveness and angiogenesis via inhibiting the activation of Rac1 and subsequently weakening its downstream effects, including F-actin polymerization and VEGF expression. Collectively, these results indicate that TIPE2 plays a key role in NSCLC metastasis, suggesting that forced TIPE2 expression might be a novel strategy for the treatment of NSCLC.
authors.affiliation: Department of Immunology, Shandong University School of Medicine, Jinan, China.
authors.forename: Zequn
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Immunology, Shandong University School of Medicine, Jinan, China.
authors.forename: Chun
authors.initials: C
authors.lastname: Guo
authors.affiliation: Department of Immunology, Shandong University School of Medicine, Jinan, China.
authors.forename: Xianglan
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Pathology, The Second Hospital of Shandong University, Jinan, China.
authors.forename: Chengjun
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Department of Immunology, Shandong University School of Medicine, Jinan, China.
authors.forename: Faliang
authors.initials: F
authors.lastname: Zhu
authors.affiliation: Department of Immunology, Shandong University School of Medicine, Jinan, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Immunology, Shandong University School of Medicine, Jinan, China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Immunology, Shandong University School of Medicine, Jinan, China.
authors.forename: Yongyu
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Immunology, Shandong University School of Medicine, Jinan, China.
authors.forename: Jianing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Immunology, Shandong University School of Medicine, Jinan, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Immunology, Shandong University School of Medicine, Jinan, China.
authors.forename: Lining
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000072283:A549 Cells; D000199:Actins / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D063646:Carcinogenesis / Q000473:pathology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008175:Lung Neoplasms / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000473:pathology*; D055503:Protein Multimerization; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
chemical_list: D000199:Actins; D014408:Biomarkers, Tumor; D047908:Intracellular Signaling Peptides and Proteins; C107953:RAC1 protein, human; C552057:TNFAIP8L2 protein, human; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D020830:rac1 GTP-Binding Protein
keywords: NSCLC; Rac1; TIPE2; angiogenesis; invasiveness