Program

PO1-6-14

Antagonistic signalling between EGFR and FGFR in HNSCC: focusing on cell migration

[Speaker] Li-Yun Chang:1
[Co-author] Chao-Yu Chu:1, Cheok-Kei Si:1, Guan-Hung Kuo:1, Feng-Chiao Tsai:1,2
1:Dept. of Pharmacology, National Taiwan University College of Medicine, Taipei, Taiwan, 2:Dept. of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

Head and neck squamous cell carcinoma (HNSCC) causes high rates of metastasis, recurrence and mortality in Taiwan, but effective treatments remain lacking. Thus searching for novel therapeutic targets against HNSCC may improve current therapeutics for HNSCC patients.
 We therefore focus on fibroblast growth factor receptor (FGFR), which is important in cancer cell proliferation, differentiation and migration. Besides, gene expression profiles from TCGA database showed that high FGFR levels in HNSCC tumors correlated with good prognosis. However, whether FGFR inhibitors affect HNSCC progression had not been explored. Thus, we used FGFR inhibitor AZD4547 to treat SAS, a head and neck squamous cell carcinoma cell line, and employed sheet migration assays. Interestingly, we found that AZD4547 suppressed the sheet migration stimulated by FGF while it slightly increased sheet migration stimulated by FBS in SAS. Such results indicated that some other growth factor interacted with FGF during cell migration. We further stimulated SAS with EGF+FGF and observed AZD4547 also slightly increased sheet migration. Thus, we proposed EGFR and FGFR signalling interacted during cell migration.
 To further explore the crosstalk between EGFR and FGFR signalling, we used single cell tracing technique to analyze how FGFR suppression changed the migration behaviors in the presence or absence of EGFR signalling. Besides AZD4547, we also knocked down FGFR2 to verify FGFR specific suppression effect. Interestingly, both AZD4547 and FGFR2 knockdown reduced the motility of SAS in the absence of EGF stimulation. However, these suppressive effects were nullified when EGF was added. Such results indicated that FGFR signalling was already suppressed when EGF was present. Moreover, when we stimulated SAS with FGF, cell migration polarity was modestly improved. Such improvement could be further magnified when we added the EGFR inhibitor AZD9291, indicating EGFR signalling might reduce polarity through FGFR suppression.
 All these results suggested that EGFR signalling might block FGFR signalling during HNSCC migration, and that suppressing EGFR signalling in HNSCC might increase FGFR signalling, resulting in the reduction of the treatment effect. We are currently working on the mechanisms how EGFR suppressed FGFR signalling, and how such signalling antagonism could be recruited for novel HNSCC therapeutics development.

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