蛋白质合成的翻译起始是基因表达的重要调节步骤，其失调可能导致癌症等疾病。 eIF4E/4E-BP 的翻译控制已得到充分研究，并有助于各种生物过程中的 mTOR 信号传导。在这里，我们报告了结肠肿瘤发生中 Wnt/β-catenin 信号通路中 eIF3a（肿瘤发生和预后中的阴阳因子）的一种新型翻译控制轴。我们发现，eIF3a 在人类结肠癌组织、癌前腺瘤息肉中表达上调，并与人类样本中的 β-catenin 水平和 APC 突变相关，并且 eIF3a 过度表达会转化肠上皮细胞。我们还表明，eIF3a 表达受 Wnt/β-catenin 信号通路的调节，其启动子中具有活性 TCF/LEF 结合位点，并且 eIF3a 敲低可抑制 APCmin/ 小鼠中 APC 突变诱导的自发结肠肿瘤发生。总之，我们得出结论，结肠癌中 eIF3a 的上调是由于 APC 突变造成的，它通过在 Wnt/β-catenin 信号通路中添加翻译控制轴来参与结肠肿瘤的发生，并且它可以作为结肠癌干预的潜在靶点。版权所有 © 2024。由 Elsevier B.V. 出版

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/4E-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 APCmin/+ 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.Copyright © 2024. Published by Elsevier B.V.