Wnt/CTNNB1 Signal Transduction Pathway Inhibits the Expression of ZFP36 in Squamous Cell Carcinoma, by Inducing Transcriptional Repressors SNAI1, SLUG and TWIST

Wnt/CTNNB1 信号转导通路通过诱导转录抑制因子 SNAI1、SLUG 和 TWIST 抑制鳞状细胞癌中 ZFP36 的表达

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作者:Emma D Zanfi, Sebastian Fantini, Roberta Lotti, Matteo Bertesi, Alessandra Marconi, Alexis Grande, Rossella Manfredini, Carlo Pincelli, Tommaso Zanocco-Marani

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.

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