The eIF3a translational control axis in the Wnt/β-catenin signaling pathway and colon tumorigenesis
Year: 2024
Type: article
Abstract: Translational initiation in protein synthesis is an important regulatory step in gene expression and its dysregulation may result in diseases such as cancer. Translational control by eIF4E/4 E -BP has been well studied and contributes to mTOR signaling in various biological processes . Here, we report a novel translational control axis in the Wnt/β-catenin signaling pathway in colon tumorigenesis by eIF3a, a Yin-Yang factor in tumorigenesis and prognosis. We show that eIF3a expression is upregulated in human colon cancer tissues, pre-cancerous adenoma polyps, and associates with β-catenin level and APC mutation in human samples, and that eIF3a overexpression transforms intestinal epithelial cells. We also show that eIF3a expression is regulated by the Wnt/β-catenin signaling pathway with an active TCF/LEF binding site in its promoter and that eIF3a knockdown inhibits APC mutation-induced spontaneous colon tumorigenesis in APC min/+ mice. Together, we conclude that eIF3a upregulation in colon cancer is due to APC mutation and it participates in colon tumorigenesis by adding a translational control axis in the Wnt/β-catenin signaling pathway and that it can serve as a potential target for colon cancer intervention.
Source: Cancer Letters
Institution: University of Toledo
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,260
OpenAlex ID: W4403411764