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bioRxiv · 10.1101/326819

Oncogenic Wnt/STOP signaling regulates ribosome biogenesis in vivo

Madan, B.·HARMSTON, N.·Nallan, G.·Montoya, A.·Faull, P.·Petretto, E.·Virshup, D. M. M.
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Abstract

Activating mutations in the Wnt pathway drive a variety of cancers, but the specific targets and pathways activated by Wnt ligands are not fully understood. To bridge this knowledge gap, we performed a comprehensive time-course analysis of Wnt-dependent signaling pathways in an orthotopic model of Wnt-addicted pancreatic cancer, using a PORCN inhibitor currently in clinical trials, and validated key results in additional Wnt-addicted models. The analysis of temporal changes following Wnt withdrawal demonstrated direct and indirect regulation of >3,500 Wnt activated genes (23% of the transcriptome). Regulation was both transcriptional via Wnt/{beta}-catenin, and through the modulation of protein abundance of important transcription factors including MYC via Wnt/STOP. Our study identifies a central role of Wnt /{beta}-catenin and Wnt/STOP signaling in controlling ribosomal biogenesis, a key driver of cancer proliferation.

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Madan, B., HARMSTON, N., Nallan, G., Montoya, A., Faull, P., Petretto, E., Virshup, D. M. M.. 2018-05-20. Oncogenic Wnt/STOP signaling regulates ribosome biogenesis in vivo. https://doi.org/10.1101/326819

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