VEGF promotes migration and invasion by regulating EMT and MMPs in nasopharyngeal carcinoma

Abstract

Background: Vascular endothelial growth factor (VEGF) is an important pro-angiogenic factor. Accumulating data have indicated that VEGF is involved in tumour metastasis. However, the mechanism through which VEGF regulates nasopharyngeal carcinoma (NPC) metastasis is largely unknown. This study aimed to examine the biological function of VEGF in NPC metastasis and its underlying mechanism. Methods: We used western blotting and qPCR to examine the difference in VEGF expression between NPC cells and the immortalized nasopharyngeal epithelial cell line NP69. Wound healing assays, transwell assays and animal experiments were used to further verify the role of VEGF in the invasion and migration of NPC cells. The protein levels of the epithelial-mesenchymal transition (EMT) and matrix metalloproteinase (MMP) family were analysed by immunofluorescence (IF) and western blotting. Enzyme-linked immunosorbent assay (ELISA) and transwell assays were used to determine whether VEGF enhanced the invasion and migration of NPC cells in an autocrine manner. Western blotting was used to examine how autocrine VEGF-VEGFR2 signalling regulated EMT and MMPs. Results: We observed higher levels of VEGF in NPC cells than that in NP69 cells and identified an association between high VEGF levels and tumour invasion and migration. Mechanistically, the VEGF-mediated increase in EMT markers, MMP2 and MMP9 promoted NPC cell invasion and migration. Additionally, NPC cells secreted VEGF to promote cell invasion, migration and angiogenesis. Autocrine VEGF-VEGFR2 signalling increased ERK1/2 phosphorylation, promoted EMT process and MMPs at the indicated times. Conclusion: This study revealed that VEGF plays a role in controlling NPC cell metastasis by regulating EMT markers and MMPs in an autocrine manner.

Exosomal LBH inhibits epithelial-mesenchymal transition and angiogenesis in nasopharyngeal carcinoma via downregulating VEGFA signaling

“…These data suggest that for nasopharyngeal carcinoma, CRYAB-dependent VEGFA expression participates in regulating EMT inhibition in LBH-elevated NPC cells induced by exosome-mediated autocrine signaling, which attenuates cellular migration and invasion. This is consistent with the views of Chen et al [46] and Schootbrugge et al [47] that both VEGFA and CRYAB promote EMT progression and metastasis in head and neck carcinoma. The exact role of VEGFA in modulating metastasis-associated phenotypes of NPC cells affected by exosome-mediated autocrine signaling, however, requires further verification by introducing VEGFA interference during exosome treatment, for example, with receptor inhibitors, neutralizing antibodies or recombinant proteins.…”

Human/eukaryotic ribosomal protein L14 (RPL14/eL14) overexpression represses proliferation, migration, invasion and EMT process in nasopharyngeal carcinoma

“…The expression of vimentin and N-cadherin are thought to facilitate the progress of cell invasion, migration, and EMT process [ 43 ]. It was reported that several genes, including vascular endothelial growth factor [ 44 ] and forkhead box 1 [ 45 ], modulated NPC migration and invasion by regulating the EMT. In this study, overexpression of RPL14(eL14) notably repressed cell migration, invasion, and EMT process in NPC cells by reducing the expression of N-cadherin and vimentin and increasing the expression of E-cadherin.…”

Microbial metabolite deoxycholic acid promotes vasculogenic mimicry formation in intestinal carcinogenesis

“…Deoxycholic acid appears to be a strong stimulant of the vascular endothelial growth factor (VEGF) expression, 56 which is demonstrated to be a vital pro–angiogenic factor involved in tumor metastasis and angiogenesis. 57 Studies have shown that abnormal secretion of VEGF binds to receptor tyrosine kinases to induce receptor dimerization and phosphorylation, particularly VEGFR1/2, resulting in the process of endothelial regeneration, angiogenesis, and induction of tumor EMT. 58 , 59 Current studies mainly focus on the relationship between VEGFR2 signaling and tumor angiogenesis, and the important role of VEGFR2 in VM formation has been neglected.…”