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.

Prognostic Significance of Trophoblastic Cell Surface Protein 2 (Trop2) Expression in Breast Cancer and Relation to Microvascular Density

“…Hence, MVD is considered as an independent prognostic factor in multiple molecular subtypes of breast cancer (Kraby et al, 2017). In the current work, Trop2 expression was significantly correlated with MVD, a finding that was consistent with Ninga, b et al (2013) and Guo et al (2017) who detected a positive correlation between Trop2 expression and tumor neovascularization in cholangiocarcinoma, glioma and non-small cell lung cancer (NSCLC), respectively. The exact mechanisms and factors enhancing pathological tumor angiogenesis are still unclear.…”

“…However, it is suggested that binding of vascular endothelial growth factor (VEGF) to its receptors stimulates intracellular pathways including extracellular signal-regulated kinase (ERK) and phosphatidyl inositol3 kinase (PI3K), which in turn enhance angiogenic switch in several malignancies including breast cancer (Taneja et al, 2010). Guo et al (2017) reported that Trop2 can stimulate angiogenesis in NSCLC via activation of extracellular signal-regulated kinase /mitogen-activated protein kinase (ERK/MPAK) pathway. Moreover, they demonstrated a reduction of angiogenic markers (CD31, CD34) expression and Ki67 proliferation index after silencing Trop2 gene in vivo.…”

Bioinformatics methods for identifying differentially expressed genes and signaling pathways in nano-silica stimulated macrophages

“…On the contrary, in order to understand the DEGs action mode, we adopted KEGG analysis, which was based on clustering similar genes into a same network, interestingly, the main action modes were cytokine–cytokine receptor interaction and transcriptional misregulation, the related signaling pathways were phosphoinositide 3-kinase (PI3K)-Akt, tumor necrosis factor (TNF), mitogen-activated protein kinase (MAPK), nuclear factor kappa B (NF-κB), RIG-I-like receptor, and Toll-like receptor (Table 2), which were consistent with previous studies in lung cancer. 14–16…”

Expression profile of tRNA‑derived fragments and their potential roles in human varicose veins

“…Tumor-associated calcium signal transducer 2 regulates neovascularization of non-small-cell lung cancer by activating the ERK1/2 signaling pathway (31). In addition, novel calcitonin gene-related peptide/chitosan-strontium-calcium phosphate cement enhances the proliferation of HUVECs (41). Furthermore, increasing extracellular Ca 2+ significantly triggers TNF-α-induced vascular cell adhesion molecule 1 activation and monocyte adhesion in HUVECs (42).…”