LAUSR.org creates dashboard-style pages of related content for over 1.5 million academic articles. Sign Up to like articles & get recommendations!

FGF9‐induced ovarian cancer cell invasion involves VEGF‐A/VEGFR2 augmentation by virtue of ETS1 upregulation and metabolic reprogramming

Photo by yuli_superson from unsplash

Ovarian cancer (OC) renders its lethality to enhanced metastasis and late detection. A plethora of growth factors including Vascular Endothelial Growth Factor (VEGF) and Fibroblast Growth Factor (FGF) stimulated signaling… Click to show full abstract

Ovarian cancer (OC) renders its lethality to enhanced metastasis and late detection. A plethora of growth factors including Vascular Endothelial Growth Factor (VEGF) and Fibroblast Growth Factor (FGF) stimulated signaling pathways regulate the invasive/metastatic behavior of ovarian tumors contributing to its aggressiveness. Autocrine VEGF‐functioning by virtue of upregulated VEGFR2 contributes to the invasiveness of OC cells by modulating the MMPs. Studies have highlighted the interaction between FGF and VEGF signaling pathways during angiogenesis. Moreover, the previous involvement of FGF9 in controlling the OC invasiveness prompted us to investigate its role in regulating VEGF‐A/VEGFR2 expression that may control the invasive behavior of the cells. Here we demonstrate that, FGF9‐induction resulted in the augmentation of VEGF‐A/VEGFR2 levels and the subsequent invasion of OC cells through the activation of the ERK‐signaling pathway. Moreover, the ETS1 transcription factor was found to enhance the VEGFA/VEGFR2 expression by directly binding to their promoters and facilitated FGF9‐dependent elevation of VEGF‐signaling which augmented the metastatic potential of OC cells. Enhanced cellular invasiveness was associated with increased aerobic glycolysis, LDH‐A expression, and lactate production. Lactate, in turn, controlled VEGF‐A/VEGFR2 expression and the resulting cell invasion. Taken together, the augmentation of VEGF‐A/VEGFR2 expression and subsequent invasion of OC cells were governed by FGF9‐dependent enhancement of both ETS1 and LDH‐A/lactate levels. Therefore, this study provides an insight into the mechanism governing elevated VEGF‐autocrine functioning in OC that contributes to its invasive/metastatic behavior.

Keywords: vegf vegfr2; invasion; augmentation; expression; vegfr2

Journal Title: Journal of Cellular Biochemistry
Year Published: 2018

Link to full text (if available)


Share on Social Media:                               Sign Up to like & get
recommendations!

Related content

More Information              News              Social Media              Video              Recommended



                Click one of the above tabs to view related content.