| Summary: | 碩士 === 國立臺灣大學 === 藥理學研究所 === 107 === Head and neck squamous cell carcinoma (HNSCC) causes high metastatic rate, recurrence rate and mortality in Taiwan, but there is still no effective treatment. We therefore aimed at finding new therapeutic targets for HNSCC and focused on the fibroblast growth factor receptor (FGFR), which is important in cancer cell proliferation, differentiation and migration. When we used FGFR inhibitor AZD4547 to treat HNSCC cells in cell migration assays, it inhibited fibroblast growth factor (FGF1)-stimulated SAS migration. However, AZD4547 did not inhibit SAS migration when FBS (fetal bovine serum) was present. Furthermore, the presence of EGF (epidermal growth factor) also abrogated the inhibitory effect of AZD4547 on SAS migration. Thus, we proposed that EGFR (epidermal growth factor receptor) and FGFR signalling interacted with each other during cell migration.
To elucidate the crosstalk between EGFR and FGFR signalling, we used single-cell tracking to analyze how FGFR/EGFR inhibition alters migration behavior in the presence or absence of the other i.e. EGFR/FGFR signalling. We found out that EGF rescued the inhibition of HNSCC cell migration by FGFR inhibitors, but EGF could not rescue FGFR2 knockdown effect. Likewise, FGF1 rescued the inhibition of HNSCC cell migration by EGFR inhibitors, but could not rescue EGFR knockdown effect.
To explain how EGFR interacts with FGFR signaling, we proposed three hypothetical models: receptor level model, transactivation model and internalization competition model. Because FGFR substrate 2a (FRS2) knockdown showed modest inhibition on EGF stimulation and western blot showed that knockdown FRS2 decreased phospho-ERK (pErk) expression, we favor transactivation model. Further investigations are underway to verify our speculations, with the hope to benefit current HNSCC treatments.
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