肝细胞癌（HCC）由于快速进展和高发生率的转移或复发而成为全球最常见的恶性肿瘤之一。越来越多的证据表明表达CD58的肿瘤细胞与各种癌症的发展有关。本研究旨在揭示CD58在HCC进展中的功能重要性及其潜在机制。使用免疫组织化学染色（IHC）和免疫印迹法检测HCC组织和细胞中CD58的表达。通过ELISA法评估细胞上清液和血清中sCD58（CD58的可溶性形式）的水平。使用CCK-8、集落形成和异种移植实验来检测CD58对体外和体内增殖的作用。进行Transwell实验和球形形成实验评估CD58和sCD58对HCC细胞转移和自我更新能力的影响。使用免疫印迹法、免疫荧光（IF）、TOP/FOP Flash报告基因测定和亚细胞分离实验来研究CD58/sCD58与AKT/GSK-3β/β-连环蛋白信号通路之间的分子调控关系。结果显示，CD58在HCC组织中明显上调。CD58表达的增加与更多的卫星灶和血管侵犯以及HCC患者的较差无肿瘤生存和总体生存相关。与健康个体相比，HCC患者的血清中sCD58水平较高。在功能上，CD58促进了体外和体内HCC细胞的增殖。同时，在体外，CD58和sCD58诱导了HCC细胞的转移、自我更新和多能性。在机制上，CD58通过增加AKT或GSK3β信号的磷酸化，激活AKT/GSK-3β/β-连环蛋白信号通路，促进了Wnt/β-连环蛋白靶标蛋白和TCF/LEF介导的转录活性的表达。此外，AKT激活剂SC-79或抑制剂LY294002消除了CD58沉默对HCC细胞增殖、转移和干细胞特性的抑制作用。综上所述，CD58通过激活AKT/GSK-3β/β-连环蛋白通路促进HCC的进展和转移，提示CD58是HCC的一种新的预后生物标志物和治疗靶点。© 2023. BioMed Central Ltd., part of Springer Nature.

Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies worldwide because of rapid progression and high incidence of metastasis or recurrence. Accumulating evidence shows that CD58-expressing tumor cell is implicated in development of various cancers. The present study aimed to reveal the functional significance of CD58 in HCC progression and the underlying mechanisms.Immunohistochemical staining (IHC), and western blotting were used to detect the expression of CD58 in HCC tissues and cells. The levels of sCD58 (a soluble form of CD58) in the cell supernatants and serum were assessed by ELISA. CCK-8, colony formation, and xenograft assays were used to detect the function of CD58 on proliferation in vitro and in vivo. Transwell assay and sphere formation assay were performed to evaluate the effect of CD58 and sCD58 on metastasis and self-renewal ability of HCC cells. Western blotting, immunofluorescence (IF), TOP/FOP Flash reporter assay, and subcellular fractionation assay were conducted to investigate the molecular regulation between CD58/sCD58 and AKT/GSK-3β/β-catenin axis in HCC cells.CD58 was significantly upregulated in HCC tissues. Elevation of CD58 expression correlated with more satellite foci and vascular invasion, and poorer tumor-free and overall survival in HCC patients. Higher sCD58 levels were in HCC patients' serum compared to healthy individuals. Functionally, CD58 promotes the proliferation of HCC cells in vitro and in vivo. Meanwhile, CD58 and sCD58 induce metastasis, self-renewal and pluripotency in HCC cells in vitro. Mechanistically, CD58 activates the AKT/GSK-3β/β-catenin signaling pathway by increasing phosphorylation of AKT or GSK3β signaling, promoting expression of Wnt/β-catenin target proteins and TCF/LEF-mediated transcriptional activity. Furthermore, AKT activator SC-79 or inhibitor LY294002 abolished the inhibitory effect of CD58 silencing on the proliferation, metastasis, and stemness of HCC cells.Taken together, CD58 promotes HCC progression and metastasis via activating the AKT/GSK-3β/β-catenin pathway, suggesting that CD58 is a novel prognostic biomarker and therapeutic target for HCC.© 2023. BioMed Central Ltd., part of Springer Nature.