Epithelial–mesenchymal transition confers resistance to selective FGFR inhibitors in SNU-16 gastric cancer cells
作者： Paulina Grygielewicz , Barbara Dymek , Anna Bujak , Pawel Gunerka , Aleksandra Stanczak
DOI: 10.1007/S10120-014-0444-1
关键词: Receptor tyrosine kinase 、 Growth factor receptor inhibitor 、 Fibroblast growth factor receptor 2 、 Mubritinib 、 Fibroblast growth factor receptor 3 、 Fibroblast growth factor receptor 、 Molecular biology 、 Biology 、 Cancer research 、 Epithelial–mesenchymal transition 、 Cancer cell
摘要: Background Up to 10 % of primary gastric cancers are characterized by FGFR2 amplification, and fibroblast growth factor receptor (FGFR) inhibitors may represent therapeutic agents for patients with these malignancies. However, long-term benefits the treatment might be limited owing occurrence drug resistance. Methods To investigate mechanisms resistance selective FGFR inhibitors, we established three FGFR2amplified SNU-16 cancer cell lines resistant AZD4547, BGJ398, PD173074, respectively. Results The (SNU-16R) demonstrated changes characteristic epithelial-to-mesenchymal transition (EMT). In addition, they displayed loss expression other tyrosine kinase receptors concurrent activation downstream signaling proteins upregulation transforming b (TGF-b) level. parental cells TGF-b1 did not evoke EMT, pharmacological inhibition TGF-b I was sufficient reverse EMT in cells. Finally, showed that SNU-16R were sensitive human epidermal 2 inhibitor mubritinib heat shock protein 90 AUY922. Conclusion conclusion, provide experimental evidence EMT-mediated emerge following or AUY922 an alternative strategy patients.
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