TRIB2 Acts Downstream of Wnt/TCF in Liver Cancer Cells to Regulate YAP and C/EBPalpha Function
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Authors
Wang, JiayiPark, Joo-Seop
Wei, Yingying
Rajurkar, Mihir
Cotton, Jennifer L.
Fan, Qishi
Lewis, Brian C.
Ji, Hongkai
Mao, Junhao
Document Type
Journal ArticlePublication Date
2013-07-25Keywords
Liver NeoplasmsIntracellular Signaling Peptides and Proteins
Wnt Signaling Pathway
Cancer Biology
Genetics and Genomics
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Show full item recordAbstract
Dysregulation of Wnt signaling is closely associated with human liver tumorigenesis. However, liver cancer-specific Wnt transcriptional programs and downstream effectors remain poorly understood. Here, we identify tribbles homolog 2 (TRIB2) as a direct target of Wnt/TCF in liver cancer and demonstrate that transcription of Wnt target genes, including TRIB2, is coordinated by the TCF and FoxA transcription factors in liver cancer cells. We show that Wnt-TRIB2 activation is critical for cancer cell survival and transformation. Mechanistically, TRIB2 promotes protein stabilization of the YAP transcription coactivator through interaction with the betaTrCP ubiquitin ligase. Furthermore, we find that TRIB2 relieves the liver tumor suppressor protein C/EBPalpha-mediated inhibition of YAP/TEAD transcriptional activation in liver cancer cells. Altogether, our study uncovers a regulatory mechanism underlying liver cancer-specific Wnt transcriptional output, and suggests that TRIB2 functions as a signaling nexus to integrate the Wnt/beta-catenin, Hippo/YAP, and C/EBPalpha pathways in cancer cells.Source
Mol Cell. 2013 Jul 25;51(2):211-25. doi: 10.1016/j.molcel.2013.05.013. Link to article on publisher's siteDOI
10.1016/j.molcel.2013.05.013Permanent Link to this Item
http://hdl.handle.net/20.500.14038/44010PubMed ID
23769673Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1016/j.molcel.2013.05.013