This GIST biology discovery from Ping Chi at MSKCC and her colleagues seems novel and important. FOXF1 is required for GIST cell growth in vitro and murine GIST growth in a model mouse. FOXF1 controls the gene expression of KIT and ETV1, and as such FOXF1 has a critical role in “enforcing the GIST cellular context for highly lineage-restricted clinical behaviour and treatment response.”
Cancer Discov. 2017 Nov 21. pii: CD-17-0468. doi: 10.1158/2159-8290.CD-17-0468. link here
The cellular context that integrates upstream signaling and downstream nuclear response dictates the oncogenic behaviour and shapes treatment responses in distinct cancer types. Here, we uncover that in GIST, the forkhead family member, FOXF1, directly controls the transcription of two master regulators, KIT and ETV1, both required for GIST precursor-interstitial cells of Cajal (ICC) lineage-specification and GIST tumorigenesis. Further, FOXF1 co-localizes with ETV1 at enhancers and functions as a pioneer factor that regulates the ETV1-dependent GIST-lineage specific transcriptome through modulation of the local chromatin context, including chromatin accessibility, enhancer maintenance and ETV1 binding. Functionally, FOXF1 is required for human GIST cell growth in vitro and murine GIST tumor growth and maintenance in vivo. The simultaneous control of the upstream signaling and nuclear response sets up a unique regulatory paradigm and highlights the critical role of FOXF1 in enforcing the GIST cellular context for highly lineage-restricted clinical behaviour and treatment response.