Flotillin-1 promotes cell growth and metastasis in oral squamous cell carcinoma.

Even to date, Oral squamous cell carcinoma (OSCC), which is one of the most common malignancies worldwide, is still a major public health problem. The cellular mechanisms underlying development of OSCC are poorly understood. Lipid rafts-associated proteins not only serve as a docking platform for protein sorting and membrane trafficking, but also coordinate signaling molecules at cell membrane to mediate intracellular responses, which makes them susceptible to be subverted by cancer cells. Although Flotillin-1 has been discovered for decades, its potential role in OSCC development is largely unknown. In current study, we demonstrate that Flotillin-1 is highly expressed in OSCC cell lines compared to normal oral epithelial cells. Modulation of Flotillin-1 expression via transfection with Flotillin-1 expression vector or shRNA showed that Flotillin-1 has a clearly positive impact on cell growth and motility in KB and/or Tca8113 cell lines. These observations were further supported by using mice or zebrafish tumor xenograft models. Mechanistic study indicated that Flotillin-1 expression activates NF-κB signaling pathway by enhancing phosphorylation of p65 and IκBα, and translocation of p65 into nucleus. Furthermore, inhibition of EGFR by AG1478 markedly repressed Flotillin-1-induced activation of NF-κB signaling pathway. Our studies suggested that Flotillin-1 plays an important role in OSCC development, and might be a potential therapeutic target for OSCC.