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.
Highlights
ZFP36 gene encodes the Zinc-finger RNA-binding protein Tristetraprolin (TTP)
ZFP36 gene is frequently downregulated in different cancers [9], where, specific mutations affecting it are not described, it seems to act as a tumor suppressor [5,10,11]
We suggest the existence of an inverse correlation between TTP and the transcriptional repressors SNAI1, SLUG and TWIST, in that they are directly targeted by TTP, but they are capable of transcriptionally repressing the expression of the ZFP36 gene
Summary
ZFP36 gene encodes the Zinc-finger RNA-binding protein Tristetraprolin (TTP). TTP expression is induced by different stimuli, such as mitogenic agents [1] and inflammation [2,3]. TTP localizes in the nucleus, but stimulation leads to its translocation in the cytosol where it recognizes and binds to specific AU motifs at the 3 UTR (AREs) of its target mRNAs, thereby triggering their degradation [4,5]. Owing to this activity, TTP is involved in the anti-inflammatory response, by targeting and inducing degradation of several pro-inflammatory cytokines mRNAs [6], thereby preventing chronical inflammation [7]. TTP has been shown to be able to revert mesenchymal to epithelial phenotype in many tumor cell lines, by down regulating the transcriptional repressors SNAI1 and TWIST1 [6]
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