Journal
JOURNAL OF CLINICAL INVESTIGATION
Volume 128, Issue 12, Pages 5620-5633Publisher
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI122383
Keywords
-
Categories
Funding
- National Research Foundation Singapore
- Singapore Ministry of Health's National Medical Research Council under the STAR Award Program
- MRC London Institute of Medical Sciences, Imperial College, London
- Singapore Ministry of Health's National Medical Research Council Open Fund-Independent Research Grant
- MRC [MC_U120097112] Funding Source: UKRI
Ask authors/readers for more resources
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 porcupine (PORCN) inhibitor currently in clinical trials, and validated key results in additional Wnt-addicted models. The temporal analysis of the drug-perturbed transcriptome demonstrated direct and indirect regulation of more than 3,500 Wnt-activated genes (23% of the transcriptome). Regulation was both via Wnt/beta-catenin and through the modulation of protein abundance of important transcription factors, including MYC, via Wnt-dependent stabilization of proteins (Wnt/STOP). Our study identifies a central role of Wnt/beta-catenin and Wnt/STOP signaling in controlling ribosome biogenesis, a key driver of cancer proliferation.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available