Signaling Pathways Supporting Tumor Invasion in Head and Neck Squamous Cell Carcinoma

Head and neck squamous cell carcinoma (HNSCC) is a highly invasive cancer. A number of signaling pathways like PI3K, Rho and TGFβ/SMAD drive the invasive nature of HNSCC. The PI3K pathway is the most altered pathway in HNSCC. Both upstream and downstream members of this pathway have been found to be mutated or overexpressed leading to an increase in cell invasion. The Rho pathway is also commonly activated; however, only overexpression or downregulation of Rho’s upstream regulators are found in HNSCC. Finally, TGFβ/SMAD pathway activation leads to epithelial mesenchymal transition in HNSCC and subsequently invasion, though loss of TGFβ/ SMAD signaling has also been shown to increase cell invasion.