2012
DOI: 10.1073/pnas.1205822109
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Canonical Wnt signaling regulates Slug activity and links epithelial–mesenchymal transition with epigenetic Breast Cancer 1, Early Onset (BRCA1) repression

Abstract: Slug (Snail2) plays critical roles in regulating the epithelial-mesenchymal transition (EMT) programs operative during development and disease. However, the means by which Slug activity is controlled remain unclear. Herein we identify an unrecognized canonical Wnt/ GSK3β/β-Trcp1 axis that controls Slug activity. In the absence of Wnt signaling, Slug is phosphorylated by GSK3β and subsequently undergoes β-Trcp1-dependent ubiquitination and proteosomal degradation. Alternatively, in the presence of canonical Wnt… Show more

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Cited by 269 publications
(248 citation statements)
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“…42 As shown in Figure 7A, expression of Ron protein was markedly diminished in mammary tissues in the absence of CD151. In line with this observation was a marked decrease in the phosphorylation at the Y654 residue of b-catenin upon CD151 removal as described in a prior study, 42 while activation of GSK-3b, crucial for Wnt signaling, remained unaffected 43,44 (Fig. 7A).…”
Section: Cd151 Removal Coincides With the Induction Of Transcriptionsupporting
confidence: 68%
“…42 As shown in Figure 7A, expression of Ron protein was markedly diminished in mammary tissues in the absence of CD151. In line with this observation was a marked decrease in the phosphorylation at the Y654 residue of b-catenin upon CD151 removal as described in a prior study, 42 while activation of GSK-3b, crucial for Wnt signaling, remained unaffected 43,44 (Fig. 7A).…”
Section: Cd151 Removal Coincides With the Induction Of Transcriptionsupporting
confidence: 68%
“…Autocrine WNT signaling regulates mammary epithelial cell fate by regulating renewal and the epithelial-to-mesenchymal transition (EMT), thereby affecting tumorigenesis and metastasis in a deregulated signaling state (7,8). Accordingly, the WNT-activated β-catenin/TCF complex potentiates breast cancer metastasis by altering the expression of genes associated with EMT (9,10).…”
Section: Introductionmentioning
confidence: 99%
“…In the nucleus, Lats2 interacts with and directly phosphorylates Snail on residue T203, supporting EMT by influencing the stability and nuclear localization of Snail (22). Glycogen synthase kinase 3b (GSK3b) phosphorylates both Slug and Snail and negatively regulates their stability thus maintaining epithelial morphology (23)(24)(25)(26)(27). The activation of oncogenic pathways, including PI3K-Akt and Ras-MAPK signaling, suppresses GSK3b activity and GSK3b-dependent reduction in Snail and Slug phosphorylation resulting in increased transcription factor stability and accumulation and EMT induction.…”
Section: Introductionmentioning
confidence: 99%