| First Author | Su Z | Year | 2018 |
| Journal | Proc Natl Acad Sci U S A | Volume | 115 |
| Issue | 32 | Pages | E7522-E7531 |
| PubMed ID | 30038030 | Mgi Jnum | J:264371 |
| Mgi Id | MGI:6194814 | Doi | 10.1073/pnas.1802422115 |
| Citation | Su Z, et al. (2018) Tumor promoter TPA activates Wnt/beta-catenin signaling in a casein kinase 1-dependent manner. Proc Natl Acad Sci U S A 115(32):E7522-E7531 |
| abstractText | The tumor promoter 12-O-tetra-decanoylphorbol-13-acetate (TPA) has been defined by its ability to promote tumorigenesis on carcinogen-initiated mouse skin. Activation of Wnt/beta-catenin signaling has a decisive role in mouse skin carcinogenesis, but it remains unclear how TPA activates Wnt/beta-catenin signaling in mouse skin carcinogenesis. Here, we found that TPA could enhance Wnt/beta-catenin signaling in a casein kinase 1 (CK1) epsilon/delta-dependent manner. TPA stabilized CK1epsilon and enhanced its kinase activity. TPA further induced the phosphorylation of LRP6 at Thr1479 and Ser1490 and the formation of a CK1epsilon-LRP6-axin1 complex, leading to an increase in cytosolic beta-catenin. Moreover, TPA increased the association of beta-catenin with TCF4E in a CK1epsilon/delta-dependent way, resulting in the activation of Wnt target genes. Consistently, treatment with a selective CK1epsilon/delta inhibitor SR3029 suppressed TPA-induced skin tumor formation in vivo, probably through blocking Wnt/beta-catenin signaling. Taken together, our study has identified a pathway by which TPA activates Wnt/beta-catenin signaling. |
