Crosstalk between KIT and FGFR3 Promotes Gastrointestinal Stromal Tumor Cell Growth and Drug Resistance.

ABSTRACT: Kinase inhibitors such as imatinib have dramatically improved outcomes for patients with gastrointestinal stromal tumor (GIST), but many patients develop resistance to these treatments. Although in some patients this event corresponds with mutations in the GIST driver oncogenic kinase KIT, other patients develop resistance without KIT mutations. In this study, we address this patient subset in reporting a functional dependence of GIST on the FGF receptor FGFR3 and its crosstalk with KIT in GIST cells. Addition of the FGFR3 ligand FGF2 to GIST cells restored KIT phosphorylation during imatinib treatment, allowing sensitive cells to proliferate in the presence of the drug. FGF2 expression was increased in imatinib-resistant GIST cells, the growth of which was blocked by RNAi-mediated silenci

SUBMITTER: Javidi-Sharifi N 

PROVIDER: S-EPMC4348216 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature