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

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.

The m6A methyltransferase WTAP plays a key role in the development of diffuse large B-cell lymphoma via regulating the m6A modification of catenin beta 1

“…A b n o r m a l l e v e l s o f W n t s i g n a l i n g h a v e b e e n implicated in the development of DLBCL (23)(24)(25)(26). Many transcriptional regulators have been demonstrated to control the transcription of CTNNB1, which is a key regulator of the Wnt/β-catenin signaling pathway (27)(28)(29)(30). Previous study indicated that m 6 A mRNA methylation regulates CTNNB1 to promote the proliferation of hepatoblastoma (31).…”

Wnt Signaling Pathways: From Inflammation to Non-Melanoma Skin Cancers

“…As described above, the stimulation of Wnt/β-catenin pathway results in Lef/Tcf transcription proteins activation, which was also studied in a mouse model of skin carcinogenesis: SCC was reduced by β-catenin/Tcf signaling inhibition [ 77 ]. Recently, the relationship between Wnt/β-catenin modulation and some transcription factors, such as Slug, Twist or Snail, was studied in order to evaluate the EMT role in cSCC; in particular, the gene ZFP36, encoding the Zinc-finger RNA-binding protein Tristetraprolin (TTP), was studied [ 78 ]. TTP is considered a tumor suppressor, thanks to its ability in arresting tumor growth and reducing the antitumor immune response of CD8+ lymphocytes.…”

“…TPP may revert EMT through the down-regulation of the transcription factors Slug, Twist and Snail, which may be induced by Wnt/β-catenin pathway and ZFP36 gene. Therefore, the Wnt/β-catenin pathway may further promote the EMT in cSCC [ 78 ].…”