Document Detail

Epithelial-mesenchymal transition confers resistance to selective FGFR inhibitors in SNU-16 gastric cancer cells.
MedLine Citation:
PMID:  25407459     Owner:  NLM     Status:  Publisher    
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 of the treatment might be limited owing to the occurrence of drug resistance.
METHODS: To investigate the mechanisms of resistance to selective FGFR inhibitors, we established three FGFR2-amplified SNU-16 gastric cancer cell lines resistant to AZD4547, BGJ398, and PD173074, respectively.
RESULTS: The resistant cell lines (SNU-16R) demonstrated changes characteristic of epithelial-to-mesenchymal transition (EMT). In addition, they displayed loss of expression of FGFR2 and other tyrosine kinase receptors concurrent with activation of downstream signaling proteins and upregulation of the transforming growth factor β (TGF-β) level. However, treatment of parental SNU-16 cells with TGF-β1 did not evoke EMT, and pharmacological inhibition of TGF-β receptor I was not sufficient to reverse EMT changes in the resistant cells. Finally, we showed that the SNU-16R cell lines were sensitive to the human epidermal growth factor receptor 2 inhibitor mubritinib and the heat shock protein 90 inhibitor AUY922.
CONCLUSION: In conclusion, we provide experimental evidence that EMT-mediated resistance might emerge in gastric cancer patients following treatment with FGFR inhibitors, and mubritinib or AUY922 treatment may be an alternative therapeutic strategy for these patients.
Paulina Grygielewicz; Barbara Dymek; Anna Bujak; Pawel Gunerka; Aleksandra Stanczak; Monika Lamparska-Przybysz; Maciej Wieczorek; Karolina Dzwonek; Daria Zdzalik
Related Documents :
10564269 - Keratocytes generate traction forces in two phases.
25486409 - Autophagosome-mediated egfr down-regulation induced by the ck2 inhibitor enhances the e...
25370819 - The synergistic effect of saha and parthenolide in mda-mb231 breast cancer cells.
20110689 - Directional cell migration and chemotaxis in wound healing response to pdgf-aa are coor...
22348829 - The anti-egfr antibody cetuximab sensitizes human head and neck squamous cell carcinoma...
22870139 - Inhibition of stat3 reverses drug resistance acquired in temozolomide-resistant human g...
19794959 - Using acetaminophen's toxicity mechanism to enhance cisplatin efficacy in hepatocarcino...
15590899 - Differential p1-purinergic modulation of human schlemm's canal inner-wall cells.
3717329 - Proliferation and differentiation of brown adipocytes from interstitial cells during co...
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-11-19
Journal Detail:
Title:  Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association     Volume:  -     ISSN:  1436-3291     ISO Abbreviation:  Gastric Cancer     Publication Date:  2014 Nov 
Date Detail:
Created Date:  2014-11-19     Completed Date:  -     Revised Date:  2014-11-20    
Medline Journal Info:
Nlm Unique ID:  100886238     Medline TA:  Gastric Cancer     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Genetic testing, prevention and health care insurance markets.
Next Document:  Prevalence and Populations of Listeria monocytogenes in Meat Products Retailed in Sao Paulo, Brazil.