| Summary: | 碩士 === 國立臺灣大學 === 藥理學研究所 === 105 === Head and neck squamous cell carcinoma (HNSCC) has high metastasis and recurrent rates and causes high cancer-related mortality in Taiwan. However, there is still no effective treatment for HNSCC. We therefore aimed to identify novel therapeutic targets to prevent HNSCC metastasis.
Mutations and amplification of FGFR (Fibroblast growth factor receptor) genes were reported to be important in cell proliferation, differentiation and migration of many cancers, including breast cancer, lung cancer and melanoma. FGFRs were also reported to be associated with epithelial–mesenchymal transition, angiogenesis and regulation of cell migration. Therefore, our question is: Does FGFR participate in HNSCC metastasis? Could it be a potential targret in curing HNSCC? To answer this question, we used shRNAs targeting FGFRs to systemically examine the effect of FGFR on HNSCC cell migration. The screen result revealed that FGFR2 knockdown significantly reduced HNSCC motility. Therefore, we proposed that FGFR2 may promote HNSCC cell migration.
To validate our hypothesis, we examined the expression level of FGFR2 in 53 tumor samples from HNSCC patients of various stages. We found that FGFR2 expression was decreased in late-stage HNSCC. To further understand the role of FGFR2 in cancer cell migration, we knocked-down, overexpressed and rescued FGFR2 levels in SAS cells, and measured how such treatments affected HNSCC cell migration. We found that FGFR2 knockdown significant decreased cell migration, probably through impairing directionality and cell-cell coordination. These results implied that FGFR2 might promote HNSCC cell migration. Interesingly, FGFR2IIIb or IIIc overexpression slightly decreased cell migration. These results suggested that there might be some interaction between FGFR2IIIb and FGFR2IIIc. Based on our findings, FGFR2 may play an important role in HNSCC metastasis. Further investigations are currently under the way to clarify the mechanism how FGFR2 changes HNSCC migration.
|
|---|
