Growth Factor Receptor Signaling and Metastasis of Oral Cancer
Growth factor receptor signaling activates a number of pathways involved in cellular proliferation and survival. Overexpression and activation of various growth factor receptors have been implicated in a number of cancers. The progression of tumor cells to an invasive phenotype requires a number of important steps, including the loss of cellular adhesion complexes and the migration of tumor cells to distant sites. These steps are regulated by growth factor receptors such as epidermal growth factor receptor (EGFR) and c-Met leading to metastasis. Overexpression and activation of EGFR lead to loss of intercellular adhesions through the downregulation of E-cadherins, desmosomes, and focal adhesion kinase. Furthermore, EGFR signaling can upregulate matrix metalloproteases (MMPs), leading to the degradation of the extracellular matrix and increased motility. Hepatocyte growth factor (HGF)/c-Met signaling can also disrupt E-cadherin expression and upregulate MMP expression, resulting in a more invasive phenotype. Thus, growth factor receptors play a major role in tumor metastasis through the regulation of key intermediary steps.
KeywordsEpidermal Growth Factor Receptor Hepatocyte Growth Factor Focal Adhesion Kinase Epidermal Growth Factor Receptor Expression Epidermal Growth Factor Receptor Inhibition
- Arteaga CL, Johnson MD, Todderud G, Coffey RJ, Carpenter G, Page DL (1991) Elevated Content of the Tyrosine Kinase Substrate Phospholipase C-1 in Primary Human Breast Carcinomas. Proc Am Assoc Cancer Res 88:10435–10439Google Scholar