Abstract
Oral squamous cell carcinoma (OSCC) is a major subtype of head and neck squamous cell carcinoma (HNSCC), and also the sixth most common cancer worldwide. In Taiwan, the etiology of OSCC is highly associated with betel nut chewing, and the number of patients suffering from OSCC has increased 18% during the past ten years. Metastasis in OSCC is rare and usually occurs at late stages. Formation of invasive and metastatic tumor is associated with poor clinical prognosis with reduced five-year survival rate. Thus, understanding the mechanisms leading to metastasis of OSCC is crucial in treating the disease. In this thesis, I used oral carcinoma 3 (OC3) cells and two invasive cell lines, OC3-I5 and OC3-IV2 cells, to study the underlying mechanisms of cancer invasiveness. Our results suggested that inhibition of MEK-ERK and PI3K-AKT pathway blocked proliferation of OC3 cells but had no significant effect on the proliferation of OC3-I5 and OC3-IV2 cells. This result suggests that OC3-I5 and OC3-IV2 cells may have gained new mechanisms to sustain proliferation. To this end, we have identified sonic hedgehog (SHH) and a number of soluble factors are involved i¬n the regulation of OC3 cell proliferation. We also found increased phosphorylation of ERK1/2 and AKT in OC3-IV2 cells compared to OC3 and OC3-I5 cells. The increased phosphorylation of ERK1/2 and AKT contributes to the increased motility of OC3-IV2 cells. Together, these findings suggest that the more invasive OC3 cell lines use different mechanisms to ensure their proliferation and migration during oral cancer progression.