ArticleMolecular cancer therapeutics2009
WIF1, a Wnt pathway inhibitor, regulates SKP2 and c-myc expression leading to G1 arrest and growth inhibition of human invasive urinary bladder cancer cells.
Article in Molecular cancer therapeutics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
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Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 102 citations in OpenAlex.
- Promoter hypermethylation of Wnt inhibitory factor-1 in patients with lung cancer: A systematic meta-analysis.Medicine · 2016Pooled it
- Reciprocal inhibition of Wnt signaling pathways pattern the interconnection of epithelial tubules in the regenerating zebrafish kidney.Development (Cambridge, England) · 2026Article
- Epigenetic regulation of human WIF1 and DNA methylation situation of WIF1 and GSTM5 in urothelial carcinoma.Heliyon · 2023Article
- The Emerging Role of RNA N6-Methyladenosine Modification in Pancreatic Cancer.Frontiers in oncology · 2022Review
- Synthetic MIR143-3p Suppresses Cell Growth in Rhabdomyosarcoma Cells by Interrupting RAS Pathways Including PAX3-FOXO1.Cancers · 2020Article
- Integrative analysis of mRNA, miRNA and lncRNA profiles reveals the commonness between bladder cancer and breast cancer.Translational cancer research · 2020Article
- Association betweenDisease markers · 2019Article
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- A novel APC mutation identified in a large Chinese family with familial adenomatous polyposis and a brief literature review.Molecular medicine reports · 2018Article
- Identification of Differentially Expressed Genes Induced by Aberrant Methylation in Oral Squamous Cell Carcinomas Using Integrated Bioinformatic Analysis.International journal of molecular sciences · 2018Article
- NDRG2 facilitates colorectal cancer differentiation through the regulation of Skp2-p21/p27 axis.Oncogene · 2018Article
- Article
- WNT signalling events near the cell membrane and their pharmacological targeting for the treatment of cancer.British journal of pharmacology · 2017Review
- The roles of ARHGAP10 in the proliferation, migration and invasion of lung cancer cells.Oncology letters · 2017Article
- Effect of perineoplasm perinephric adipose tissues on migration of clear cell renal cell carcinoma cells: a potential role of WNT signaling.Oncotarget · 2016Article
- PTBP1-associated microRNA-1 and -133b suppress the Warburg effect in colorectal tumors.Oncotarget · 2016Article
- Curcumin Inhibits 3T3-L1 Preadipocyte Proliferation by Mechanisms Involving Post-transcriptional p27 Regulation.Biochemistry and biophysics reports · 2016Article
- MicroRNA-224 sustains Wnt/β-catenin signaling and promotes aggressive phenotype of colorectal cancer.Journal of experimental & clinical cancer research : CR · 2016Article
- A novel cell-penetrating peptide suppresses breast tumorigenesis by inhibiting β-catenin/LEF-1 signaling.Scientific reports · 2016Article
- Regulation of metastasis of bladder cancer cells through the WNT signaling pathway.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015Article
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
Epigenetic silencing of secreted wingless-type (Wnt) antagonists through hypermethylation is associated with tobacco smoking and with invasive bladder cancer. The secreted Wnt inhibitory factor-1 (WIF1) has shown consistent growth-inhibitory effect on various cancer cell lines. Therefore, we assessed the mechanisms of action of WIF1 by either restoring WIF1 expression in invasive bladder cancer cell lines (T24 and TSU-PR1) or using a recombinant protein containing functional WIF1 domain. Both ectopic expression of WIF1 and treatment with WIF1 domain protein resulted in cell growth inhibition via G(1) arrest. The G(1) arrest induced by WIF1 is associated with down-regulation of SKP2 and c-myc and up-regulation of p21/WAF1 and p27/Kip1. Conversely, reexpression of SKP2 in WIF1-overexpressing TSU-PR1 cells attenuated the WIF1-induced G(1) arrest. Furthermore, inhibition of nuclear Wnt signaling by either dominant-negative LEF1 or short hairpin RNA of TCF4 also reduced SKP2 expression. The human SKP2 gene contains two TCF/LEF1 consensus binding sites within the promoter. Chromatin immunoprecipitation/real-time PCR analysis revealed that both WIF1 and dominant-negative LEF1 expression decreased the in vivo binding of TCF4 and beta-catenin to the SKP2 promoter. Together, our results suggest that mechanisms of WIF1-induced G(1) arrest include (a) SKP2 down-regulation leading to p27/Kip1 accumulation and (b) c-myc down-regulation releasing p21/WAF1 transcription. Additionally, we show that WIF1 inhibits in vivo bladder tumor growth in nude mice. These observations suggest a mechanism for transformation of bladder epithelium on loss of WIF1 function and provide new targets such as SKP2 for intervention in WIF1-deficient bladder cancer.
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