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Translation cooperation of FGF and WNT signaling

ABSTRACT: Cooperation between FGF and WNT signaling is well documented in normal development, stem cell biology and cancer progression. However, the molecular mechanisms underlying this cooperativity remain poorly understood. In this study, we employed an inducible FGFR1 to interrogate the dynamics of RNA, ribosome occupancy and protein expression as a function of FGFR signaling in the mouse mammary gland with constitutive WNT hyperactivation. We demonstrate that FGFR signaling increases the translation efficiency of WNT signaling components with structured 5’ UTRs harboring a (CGG)4 motif that can potentially form G-quadruplex structures, and that tumorigenesis driven by this mechanism is vulnerable to inhibition of eIF4A, a RNA helicase important in translation initiation. This study also provides novel insights into the contribution of RNA levels and translational regulation to protein expression in pre-malignant mammary epithelial cells dynamically responding to FGFR signaling.

ORGANISM(S): Mus musculus

PROVIDER: GSE107926 | GEO | 2018/05/29

REPOSITORIES: GEO

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