FGFR signalling promotes the growth of triple negative and basal-like breast cancer cell lines both in vitro and in vivo
Menée sur 31 lignées cellulaires de cancer du sein et à l'aide de xénogreffes, cette étude montre que la signalisation FGFR favorise la croissance des cancers du sein triple négatif et basal-like
Purpose: The oncogenic drivers of triple negative and basal-like breast cancers are largely unknown. Substantial evidence now links aberrant signalling by the fibroblast growth factor receptors (FGFRs) to the development of multiple cancer types. Here, we examined the role of FGFR signalling in triple negative breast cancer. Experimental design: We examined the sensitivity of a panel of 31 breast cancer cell lines to the selective fibroblast growth factor receptor (FGFR) inhibitor PD173074 and investigated the potential mechanisms underlying sensitivity. Results: Triple negative (TN) breast cancer cell lines were more sensitive to PD173074 than comparator cell lines (p=0.011) with 47% (7/15) of TN cell lines demonstrating significantly reduced growth. The majority of TN cell lines demonstrated only modest sensitivity to FGFR inhibition in two-dimensional growth, but were highly sensitive in anchorage independent conditions. PD173074 inhibited downstream MAPK and PI3K-AKT signalling and induced cell cycle arrest and apoptosis. Basal-like breast cancer cell lines were found to express FGF2 ligand (11/21 positive), and similarly 62% of basal-like breast cancers expressed FGF2 as assessed by immunohistochemistry compared to 5% of non-basal breast cancers (p<0.0001). RNA interference targeting of FGF2 in basal-like cell lines significantly reduced growth in vitro and reduced down stream signalling, suggesting an autocrine FGF2 signalling loop. Treatment with PD173074 significantly reduced the growth of CAL51 basal-like breast cancer cell line xenografts in vivo. Conclusions: Basal-like breast cancer cell lines and breast cancers express autocrine FGF2 and demonstrate sensitivity to FGFR inhibitors, identifying a potential novel therapeutic approach for these cancers.