title: Tumor-associated calcium signal transducer 2 regulates neovascularization of non-small-cell lung cancer via activating ERK1/2 signaling pathway.
abstract: Lung cancer, especially the non-small-cell lung cancer, is a highly aggressive vascular cancer with excessively activated signaling pathways. Tumor-associated calcium signal transducer 2, also known as trop2, was identified to be correlated with tumor proliferation and invasion of non-small-cell lung cancer; however, the biological role of trop2 in neovascularization of non-small-cell lung cancer remained elusive. In this study, we first verified that trop2 was overexpressed in non-small-cell lung cancer tissues as well as cell lines and that the increased expression of trop2 promoted non-small-cell lung cancer cell proliferation and invasion. Then, we expanded the biological role of trop2 by in vitro and in vivo angiogenesis assay. The tubular formation analysis revealed that trop2 promoted non-small-cell lung cancer angiogenesis in vitro, and the immunohistochemistry staining of vascular markers (CD31 and CD34) provided evidences that trop2 promoted in vivo neovascularization. The results of polymerase chain reaction array revealed that trop2 promoted the expression level of two well-known angiogenesis factors MMP13 and PECAM1. By screening the trop2-related signaling pathways, we observed that excessive angiogenesis was correlated with activation of ERK1/2 signaling pathway, and ERK1/2 inhibitor (U0126) could suppress the tubular formation ability induced by trop2 expression. These results suggested that trop2 facilitated neovascularization of non-small-cell lung cancer via activating ERK1/2 signaling pathway. Targeting trop2 might provide novel anti-angiogenesis strategy for non-small-cell lung cancer treatment.
authors.affiliation: 1 Department of Respiratory Disease, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou, China.
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Guo
authors.affiliation: 2 Department of Thoracic Surgery, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Zhu
authors.affiliation: 1 Department of Respiratory Disease, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou, China.
authors.forename: Limin
authors.initials: L
authors.lastname: Zhao
authors.affiliation: 1 Department of Respiratory Disease, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Li
authors.affiliation: 1 Department of Respiratory Disease, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou, China.
authors.forename: Dongjun
authors.initials: D
authors.lastname: Cheng
authors.affiliation: 1 Department of Respiratory Disease, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou, China.
authors.forename: Keqing
authors.initials: K
authors.lastname: Feng
mesh_terms: D000072283:A549 Cells; D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism*; D002070:Butadienes / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D045744:Cell Line, Tumor; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000473:pathology*; D009570:Nitriles / Q000494:pharmacology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis; D016133:Polymerase Chain Reaction; D017434:Protein Structure, Tertiary
chemical_list: D000951:Antigens, Neoplasm; D002070:Butadienes; D015815:Cell Adhesion Molecules; D009570:Nitriles; D019408:Platelet Endothelial Cell Adhesion Molecule-1; C499380:TACSTD2 protein, human; C113580:U 0126; D048049:Extracellular Signal-Regulated MAP Kinases; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; D002118:Calcium
keywords: ERK1/2; Trop2; neovascularization; non-small-cell lung cancer