Xiong, P., Xiao, L.Y., Yang, R., Guo, Q., Zhao, Y.Q., Li, W., and Yong, S. (2013) Flotillin-1 promotes cell growth and metastasis in oral squamous cell carcinoma. Neoplasma. 60(4):395-405.
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.