The role of FGFR1 signaling in cancer

Abstract

Fibroblast growth factors (FGFs), master regulators of cell functions, activate intracellular signaling cascades through binding fibroblast growth factor receptors (FGFRs). The aberrant FGFR signaling is often correlated with misregulation of oncogenes and tumorigenesis. Previous study in the laboratory has demonstrated FGFRs as potential therapeutic target of breast cancer and bone sarcoma. In this study, mechanisms of FGF/FGFR signaling in these cancers were further investigated. Western Blot was the chief technique performed to probe protein expression and its phosphorylation status. Both breast cancer and normal breast cancer cells were responsive to FGF2 and transduced signal mainly through ERK1/2 but not AKT pathway. In contrast, osteosarcoma was responsive to FGF2 stimulus but not osteoblast, suggesting that FGF/FGFR signaling differentially affects different tissues. Blockage of FGF2-activated ERK1/2 pathway by U0126 had significantly decreased cell cycle regulators-Cyclin D1 and p21 in breast cancer cells but not in normal breast cells. Although phosphorylated-p53 tumor suppressor and apoptotic protein Bim were increased in all cells, U0126 had increased p53 in breast cancer but not in the normal breast cells. This study has suggested an important role of FGF/FGFR/ERK signaling in cancer cell growth and survival leading to tumor development.