Abstract
The Wnt/CTNNB1 pathway is often deregulated in epithelial tumors. The ZFP36 gene, encoding the mRNA binding protein Tristetraprolin (TTP), is downregulated in several cancers, where it has been described to behave as a tumor suppressor. By this report, we show that Wnt/CTNNB1 pathway is constitutively activated, and ZFP36 expression is downregulated in Squamous Cell Carcinoma (SCC) cell lines compared to normal keratinocytes. Moreover, we suggest that the decrease of ZFP36 expression might depend on the activity of transcriptional repressors SNAI1, SLUG and TWIST, whose expression is induced by Wnt/CTNNB1, highlighting a potential regulatory mechanism underlying ZFP36 downregulation in epithelial cancers.
Keywords:
EMT; Wnt/CTNNB1 signaling pathway; ZFP36; squamous cell carcinoma; transcriptional repressors.
MeSH terms
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Base Sequence
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Carcinoma, Squamous Cell / genetics
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Carcinoma, Squamous Cell / metabolism*
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Carcinoma, Squamous Cell / pathology
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Cell Line, Tumor
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Down-Regulation / drug effects
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Down-Regulation / genetics
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Gene Expression Regulation, Neoplastic / drug effects
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Genome, Human
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Humans
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Keratinocytes / metabolism
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
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Promoter Regions, Genetic / genetics
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Repressor Proteins / metabolism*
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Snail Family Transcription Factors / genetics
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Snail Family Transcription Factors / metabolism*
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Sulfonamides / pharmacology
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Tristetraprolin / genetics
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Tristetraprolin / metabolism*
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Twist-Related Protein 1 / genetics
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Twist-Related Protein 1 / metabolism*
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Up-Regulation / drug effects
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Wnt Signaling Pathway* / drug effects
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Wnt Signaling Pathway* / genetics
Substances
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FH535
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Nuclear Proteins
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Repressor Proteins
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SNAI1 protein, human
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Snail Family Transcription Factors
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Sulfonamides
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TWIST1 protein, human
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Tristetraprolin
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Twist-Related Protein 1
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ZFP36 protein, human