肝癌，主要是肝细胞癌，是一个重大的全球健康问题，具有重大的临床、经济和心理影响。由于乙型和丙型肝炎感染、非酒精性脂肪性肝炎以及各种环境影响等危险因素，其发病率持续上升。 Wnt/β-Catenin 信号通路在 HCC 中经常失调，成为一个有前途的治疗靶点。关键的遗传改变，特别是 CTNNB1 基因中的突变，涉及 β-连环蛋白 N 末端结构域（S33、S37、T41 和 S45）和犰狳重复结构域（K335I 和 N387 K）的关键磷酸化位点的突变。这些突变阻碍 β-连环蛋白降解，增强其致癌潜力。除了遗传改变外，分子和表观遗传机制（包括 DNA 甲基化、组蛋白修饰和非编码 RNA）进一步影响 β-连环蛋白信号传导和肿瘤进展。然而，仅β-连环蛋白激活不足以促进肝癌发生。肿瘤的发生需要额外的基因“打击”。 Ras、c-Met、NRF2 和 LKB1 等基因的突变或改变与 β-连环蛋白激活相结合，可显着促进 HCC 的发生和进展。了解这些协同突变可以提供对该疾病的重要见解并揭示潜在的治疗策略。遗传变异和肿瘤微环境之间复杂的相互作用，加上针对 Wnt/β-Catenin 通路的新型治疗方法，为改善 HCC 治疗提供了希望。尽管取得了进展，但将临床前研究结果转化为临床实践仍然是一个挑战。未来的研究应侧重于阐明特定的 β-连环蛋白突变和其他基因改变如何导致 HCC 发病机制，利用基因改造的小鼠模型探索不同的信号传导影响，并确定下游靶标。相关临床试验对于推进个性化治疗和改善患者治疗效果至关重要。本综述对 HCC 中的 β-连环蛋白信号传导进行了全面分析，强调了其在发病机制、诊断和治疗靶向中的作用，并确定了关键研究方向以提高理解和临床结果。

Liver cancer, primarily hepatocellular carcinoma, represents a major global health issue with significant clinical, economic, and psychological impacts. Its incidence continues to rise, driven by risk factors such as hepatitis B and C infections, nonalcoholic steatohepatitis, and various environmental influences. The Wnt/β-Catenin signaling pathway, frequently dysregulated in HCC, emerges as a promising therapeutic target. Critical genetic alterations, particularly in the CTNNB1 gene, involve mutations at key phosphorylation sites on β-catenin's N-terminal domain (S33, S37, T41, and S45) and in armadillo repeat domains (K335I and N387 K). These mutations impede β-catenin degradation, enhancing its oncogenic potential. In addition to genetic alterations, molecular and epigenetic mechanisms, including DNA methylation, histone modifications, and noncoding RNAs, further influence β-catenin signaling and tumor progression. However, β-catenin activation alone is insufficient for hepatocarcinogenesis; additional genetic "hits" are required for tumor initiation. Mutations or alterations in genes such as Ras, c-Met, NRF2, and LKB1, when combined with β-catenin activation, significantly contribute to HCC development and progression. Understanding these cooperative mutations provides crucial insights into the disease and reveals potential therapeutic strategies. The complex interplay between genetic variations and the tumor microenvironment, coupled with novel therapeutic approaches targeting the Wnt/β-Catenin pathway, offers promise for improved treatment of HCC. Despite advances, translating preclinical findings into clinical practice remains a challenge. Future research should focus on elucidating how specific β-catenin mutations and additional genetic alterations contribute to HCC pathogenesis, leveraging genetically clengineered mouse models to explore distinct signaling impacts, and identifying downstream targets. Relevant clinical trials will be essential for advancing personalized therapies and enhancing patient outcomes. This review provides a comprehensive analysis of β-Catenin signaling in HCC, highlighting its role in pathogenesis, diagnosis, and therapeutic targeting, and identifies key research directions to improve understanding and clinical outcomes.