A Wnt–Axin2–GSK3β cascade regulates Snail1 activity in breast cancer cells

Yook, Jong In; Li, Xiao Yan; Ota, Ichiro; Hu, Casey Yuexian; Kim, Hyun Sil; Kim, Nam Hee; Young, So; Ryu, Joo Kyung; Choi, Yoon Jung; Kim, Jin; Fearon, Eric R.; Weiss, Stephen J.

doi:10.1038/ncb1508

Cited by 567 publications

(622 citation statements)

References 30 publications

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“…Tumor invasion and EMT are associated with Wnt activation by regulating the b-catenin/E-cadherin complex (Nelson and Nusse, 2004). Moreover, the b-catenin/TCF complex that is induced by the canonical Wnt pathway enhanced the Axin2-dependent pathway and increased stabilization of Snail, a critical regulator of EMT (Yook et al, 2006). Id-1 is also involved in tumor angiogenesis and invasion/ metastasis (Ling et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Id-1 activates Akt-mediated Wnt signaling and p27Kip1 phosphorylation through PTEN inhibition

et al. 2008

Oncogene

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Inhibitor of differentiation-1 (Id-1) has been accepted as a putative oncogene to promote oncogenic processes through inactivation of tumor suppressors and activation of growth promoting pathways. Here, we show that Id-1 activates the Akt pathway by inhibition of phosphatase and tensin homologue deleted on chromosome 10 (PTEN) transcription through downregulation of p53. Id-1 negatively regulated both p53 and PTEN at the transcriptional level. In promoter assay with serial deletion and chromatin immunoprecipitation assay, the binding of p53 to the PTEN promoter was reduced by Id-1, suggesting that Id-1 regulates PTEN transcription through its p53 modulation. This led to Akt phosphorylation at Ser473 and the activation of the Akt-mediated canonical Wnt signaling pathway. The glycogen synthase kinase-3b phosphorylation at Ser9, stabilization and nuclear localization of b-catenin, T-cell factor (TCF)/lymphoid enhancer factor transactivation activity and cyclin D1 expression were enhanced by Id-1. On the other hand, Akt-mediated p27 Kip1 phosphorylation at Thr157 and its cytosolic localization were also increased in Id-1 overexpressing MCF7 cells. In conclusion, our results disclose Id-1 as a novel PTEN inhibitor that could activate the Akt pathway and its downstream effectors, the Wnt/TCF pathway and p27 Kip1 phosphorylation and suggest that the oncogenic function of Id-1 may be partly attributed to its PTEN inhibition in human breast carcinogenesis.

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Section: Discussionmentioning

confidence: 99%

Id-1 activates Akt-mediated Wnt signaling and p27Kip1 phosphorylation through PTEN inhibition

et al. 2008

Oncogene

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“…Given the multiplicity of cytokines, growth factors, matrix degradation products, and lipid mediators found within the proinflammatory environment that characterizes RA (1-4), it will likely prove difficult to identify a dominant MT1-MMP regulator (50). Indeed less "classical" inflammatory mediators such as hypoxia, HIF-2b, Wnt family members, or epigenetic changes in DNA methylation may well serve as dominant players in the control of MT1-MMP expression or activity in RA (64)(65)(66)(67)(68)(69). Nevertheless, given the expression of MT1-MMP within RA synoviocytes at sites of tissue damage in vivo, its pathophysiologically relevant functional properties, and the recent development of MT1-MMP-specific inhibitors (70), the proteinase could serve as an important target for therapeutic intervention.…”

Section: Discussionmentioning

confidence: 99%

Membrane-Type I Matrix Metalloproteinase-Dependent Regulation of Rheumatoid Arthritis Synoviocyte Function

Sabeh¹,

Fox

Weiss³

2010

The Journal of Immunology

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“…Activation of Wnt/b-catenin signaling in cancer often drives a transcriptional program such as transcriptional repressor of Ecadherin, Snail that is reminiscent of an EMT, which can promote cell migration and invasiveness (5). The dysregulation of the Wnt/b-catenin pathway has been observed in various forms of cancer.…”

Section: Introductionmentioning

confidence: 99%

miR-483-5p Promotes Invasion and Metastasis of Lung Adenocarcinoma by Targeting RhoGDI1 and ALCAM

et al. 2014

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The nodal regulatory properties of microRNAs (miRNA) in metastatic cancer may offer new targets for therapeutic control. Here, we report that upregulation of miR-483-5p is correlated with the progression of human lung adenocarcinoma. miR-483-5p promotes the epithelial-mesenchymal transition (EMT) accompanied by invasive and metastatic properties of lung adenocarcinoma. Mechanistically, miR-483-5p is activated by the WNT/b-catenin signaling pathway and exerts its prometastatic function by directly targeting the Rho GDP dissociation inhibitor alpha (RhoGDI1) and activated leukocyte cell adhesion molecule (ALCAM), two putative metastasis suppressors. Furthermore, we found that downregulation of RhoGDI1 enhances expression of Snail, thereby promoting EMT. Importantly, miR-483-5p levels are positively correlated with b-catenin expression, but are negatively correlated with the levels of RhoGDI1 and ALCAM in human lung adenocarcinoma. Our findings reveal that miR-483-5p is a critical b-catenin-activated prometastatic miRNA and a negative regulator of the metastasis suppressors RhoGDI1 and ALCAM. Cancer Res; 74(11); 3031-42. Ó2014 AACR.

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A Wnt–Axin2–GSK3β cascade regulates Snail1 activity in breast cancer cells

Cited by 567 publications

References 30 publications

Id-1 activates Akt-mediated Wnt signaling and p27Kip1 phosphorylation through PTEN inhibition

Id-1 activates Akt-mediated Wnt signaling and p27Kip1 phosphorylation through PTEN inhibition

Membrane-Type I Matrix Metalloproteinase-Dependent Regulation of Rheumatoid Arthritis Synoviocyte Function

miR-483-5p Promotes Invasion and Metastasis of Lung Adenocarcinoma by Targeting RhoGDI1 and ALCAM

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