纖維母細胞生長因子受器第三型對頭頸部鱗狀上皮細胞癌細 胞遷移與癌症病程的影響

Fibroblast growth factor receptor 3 affects cell migration and cancer progression in head and neck squamous cell carcinoma

郭冠宏(Guan-Hung Kuo)

指導教授 ： 蔡丰喬

國立臺灣大學/醫學院/藥理學研究所/碩士(2016年)

https://doi.org/10.6342/NTU201603057

摘要

無資料

關鍵字

頭頸癌 ； FGFR3 ； 癌症轉移 ； 細胞遷移 ； 異構體轉換

並列摘要

Head and neck squamous cell carcinoma (HNSCC) causes significantly high morbidity and mortality in Taiwan, but effective treatments remain lacking. Therefore, our specific aim is to identify novel therapeutic targets against the progression of HNSCC. Fibroblast growth factor receptor 3 (FGFR3), a tyrosine kinase receptor, is critical for embryogenesis, wound healing and angiogenesis. Its aberrant expression causes developmental disorders and several cancers, including multiple myeloma, bladder cancer and prostate cancer. Recent reports suggested that differential expression of FGFR3 isoforms was linked to tumor progression in colorectal and pancreatic cancers. However, whether and how FGFR3 contributes to HNSCC progression is not known. To answer these questions, we examined the expression levels of FGFR3 isoforms in HNSCC from patients of different clinical stages. We found that in late stages of HNSCC, the expression levels of FGFR3 went up slightly. Among the isoforms, FGFR3IIIc isoform was slightly decreased, but FGFR3IIIb isoform did not change during tumor progression. These results were different from previous reports about FGFR3 in other cancers. We therefore perturbed FGFR3 activities in HNSCC cell lines to observe their effects on cell migration. Our results showed that FGFR3 knockdown increased cell migration, and that FGFR3IIIb overexpression reduced cell motility and decreased ERK & AKT signaling. However, FGFR3IIIc manipulation showed no effects on cell migration. These results imply that FGFR3IIIb suppresses HNSCC progression. In the meantime, our results also revealed that (1) effects of FGFR inhibitors on cell migration were regulated by other receptor signaling, such as epithelial growth factor receptor (EGFR), and (2) FGFR2 inhibition reduced cell motility. Though these in vitro data were not totally consistent with clinical data, our findings suggest that FGFR3 has complicated interactions with FGFR2 and other signal transduction molecules. Further investigation is needed to clarify these puzzles

並列關鍵字

Head and neck cancer ； FGFR3 ； cancer metastasis ； cell migration ； isoform switch

參考文獻

39. Holzmann, K., et al., Alternative Splicing of Fibroblast Growth Factor Receptor IgIII Loops in Cancer. J Nucleic Acids, 2012. 2012: p. 950508.

54. Matsuda, Y., J. Ueda, and T. Ishiwata, Fibroblast growth factor receptor 2: expression, roles, and potential as a novel molecular target for colorectal cancer. Patholog Res Int, 2012. 2012: p. 574768.

3. Blot, W.J., et al., Smoking and drinking in relation to oral and pharyngeal cancer. Cancer Res, 1988. 48(11): p. 3282-7.

4. Warnakulasuriya, S., Areca nut use: an independent risk factor for oral cancer. British Medical Journal, 2002.

5. Sathish, N., X. Wang, and Y. Yuan, Human Papillomavirus (HPV)-associated Oral Cancers and Treatment Strategies. J Dent Res, 2014. 93(7 Suppl): p. 29S-36S.