Romanowicz Adrianna, Łukaszewicz-Zając Marta
Department of Biochemical Diagnostics, Medical University of Bialystok, Waszyngtona 15a, 15-269 Białystok, Poland.
Department of Neurodegeneration Diagnostics, Medical University of Bialystok, Waszyngtona 15a, 15-269 Bialystok, Poland.
Int J Mol Sci. 2025 Aug 22;26(17):8130. doi: 10.3390/ijms26178130.
The Wntβ-catenin signaling pathway is a key regulator of gastrointestinal (GI) tumorigenesis, modulating cellular processes such as proliferation, differentiation, and epithelial-to-mesenchymal transition (EMT). In this review, we evaluate the expression and mutation profiles of core Wntpathway components in the most common GI malignancies. Our findings outline notable alterations in ligands, receptors, co-receptors, and intracellular effectors across different GI cancers. In gastric cancer tissue, elevated levels of Wnt proteins, FZD7 receptor, and LRP5/6, along with β-catenin accumulation and reduced APC expression, are associated with poor prognosis. In colorectal cancer samples, common APC mutations and Wnt ligand overexpression contribute to β-catenin nuclear localization and EMT. Esophageal cancer specimens exhibit co-overexpression of Wnt2 and Wnt5A, as well as receptors such as FZD2 and FZD6, which are linked to worse prognosis and reduced survival. Liver cancer tissue commonly harbors CTNNB1 mutations, which encode β-catenin and are associated with poor differentiation. In pancreatic cancer samples, overexpression of Wnt ligands, FZD receptors, and β-catenin is associated with the presence of distant metastasis and poor clinical outcomes. In conclusion, this pathway represents a promising avenue for identifying novel diagnostic, prognostic, and therapeutic biomarkers in GI cancers, warranting further clinical investigation.
Wntβ-连环蛋白信号通路是胃肠道（GI）肿瘤发生的关键调节因子，可调节细胞增殖、分化和上皮-间质转化（EMT）等细胞过程。在本综述中，我们评估了最常见的胃肠道恶性肿瘤中Wnt信号通路核心成分的表达和突变情况。我们的研究结果概述了不同胃肠道癌症中配体、受体、共受体和细胞内效应器的显著变化。在胃癌组织中，Wnt蛋白、FZD7受体和LRP5/6水平升高，以及β-连环蛋白积累和APC表达降低，与预后不良相关。在结直肠癌样本中，常见的APC突变和Wnt配体过表达导致β-连环蛋白核定位和EMT。食管癌标本显示Wnt2和Wnt5A以及FZD2和FZD6等受体共同过表达，这与较差的预后和生存率降低有关。肝癌组织通常存在CTNNB1突变，该突变编码β-连环蛋白，与低分化有关。在胰腺癌样本中，Wnt配体、FZD受体和β-连环蛋白的过表达与远处转移的存在和不良临床结果相关。总之，该通路是识别胃肠道癌症新的诊断、预后和治疗生物标志物的有前景的途径，值得进一步临床研究。
