Epidermal Growth Factor-Induced Pyruvate Dehydrogenase Kinase 1 Enhances Head And Neck Squamous Cell Carcinoma Metastasis Through Fibronectin Up-Regulation

Epidermal growth factor receptor (EGFR) activation is a major cause of metastasis in many cancers, such as head and neck squamous cell carcinoma (HNSCC). However, whether the induction of pyruvate dehydrogenase kinase 1 (PDK1) mediates EGF-enhanced HNSCC metastasis remains unclear. Interestingly, we found that EGF induced PDK1 expression in HNSCC. The tumor cell transformation induced by EGF was repressed by the depletion of PDK1. The down-regulation of PDK1 expression or inhibition of its activity significantly blocked EGF-enhanced cell migration and invasion. In addition, depletion of PDK1 impeded EGF-enhanced binding of HNSCC cells to endothelial cells and tumor cells metastastic seeding of the lungs. Knockdown of PDK1 also inhibited EGF-induced matrix metalloproteinase-1 (MMP-1), MMP-2, MMP-3, MMP-9, and fibronectin expression and Rac1/cdc42 activation. These results demonstrate that EGF-induced PDK1 expression enhances HNSCC metastasis via activation of the fibronectin signaling pathway. The inhibition of PDK1 may be a potential strategy for the treatment of EGFR-mediated HNSCC metastasis. Citation Format: Ben-Kuen Chen, Jinn-Yuan Hsu, Wen-Chang Chang. Epidermal growth factor-induced pyruvate dehydrogenase kinase 1 enhances head and neck squamous cell carcinoma metastasis through fibronectin up-regulation. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 710.