FAP通过与ITGB1相互作用激活PI3K/AKT通路，促进口腔白斑的进展

IF 5 2区医学 Q2 Medicine

Translational Oncology Pub Date : 2025-09-12 DOI:10.1016/j.tranon.2025.102531

Ran Li , Tiantian Liu , Yixuan Gu , Yuantao Gao , Xiaofeng Jiao , Yanwei Li , Songqingmeng Tian , Kejie Cao

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引用次数: 0

摘要

目的探讨成纤维细胞活化蛋白（FAP）参与口腔白斑（OLK）恶性发展的分子机制。方法通过免疫组织化学方法评估不同级别（轻度、中度和重度）的人OLK和口腔鳞状细胞癌（OSCC）组织中fap的表达。转染DOK和SCC15细胞系以调节FAP表达，随后进行功能测定，包括菌落形成、细胞活力、跨井迁移和伤口愈合。Western blot检测整合素β1 (ITGB1) /PI3K/AKT通路相关蛋白的表达。在体内，fap敲低试剂被施用于小鼠模型的OLK病变。采用苏木精和伊红（HE）染色评估异常增生和OSCC的发生率，免疫组化（IHC）检测FAP和p-AKT的表达。结果fap、p-AKT表达水平与OLK发育不良严重程度呈正相关。机制研究表明，FAP通过激活ITGB1/PI3K/AKT信号通路来增强恶性行为，如增殖和迁移。重要的是，在小鼠模型中，FAP的抑制显著降低了口腔上皮发育不良和OSCC的发生率。结论fap通过ITGB1/PI3K/AKT信号轴促进OLK的进展，其抑制作用减弱了恶性转化。本研究强调了FAP在OLK恶性转化中的重要作用，为早期诊断和针对性干预提供了新的理论依据。FAP的表达水平与OLK发育不良的程度呈正相关，表明其作为评估恶性转化风险的生物标志物的潜在效用。此外，针对FAP或ITGB1/PI3K/AKT信号通路的治疗方法可能会延迟或阻止OLK向OSCC的进展，为临床实践中精准医疗策略的发展提供了有希望的途径。

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FAP promotes progression of oral leukoplakia via activation of PI3K/AKT pathway by interacting with ITGB1

Objective

This study aims to elucidate the molecular mechanisms by which fibroblast activation protein (FAP) contributes to the malignant progression of oral leukoplakia (OLK).

Methods

FAP expression was assessed via immunohistochemistry in human OLK and oral squamous cell carcinoma (OSCC) tissues across varying grades of dysplasia (mild, moderate, and severe). DOK and SCC15 cell lines were transfected to modulate FAP expression, followed by functional assays including colony formation, cell viability, transwell migration, and wound healing. Western blot analysis was performed to evaluate the expression of proteins involved in the integrin β1 (ITGB1) /PI3K/AKT pathway. In vivo, FAP-knockdown reagents were administered to OLK lesions in a murine model. Hematoxylin and eosin (HE) staining was used to assess the incidence of dysplasia and OSCC, while immunohistochemistry (IHC) was employed to examine FAP and p-AKT expression.

Results

FAP and p-AKT expression levels were positively correlated with the severity of dysplasia in OLK. Mechanistic investigations revealed that FAP enhances malignant behaviors such as proliferation and migration through activation of the ITGB1/PI3K/AKT signaling pathway. Importantly, suppression of FAP significantly reduced the incidence of both oral epithelial dysplasia and OSCC in the mouse model.

Conclusion

FAP facilitates the progression of OLK via the ITGB1/PI3K/AKT signaling axis, and its suppression attenuates malignant transformation.

Clinical significance

This study highlights the critical involvement of FAP in the malignant transformation of OLK, offering new theoretical foundations for early diagnosis and targeted intervention. The expression level of FAP is positively correlated with the degree of OLK dysplasia, indicating its potential utility as a biomarker for evaluating malignant transformation risk. Moreover, therapeutic approaches targeting FAP or the ITGB1/PI3K/AKT signaling pathway may delay or prevent the progression of OLK to OSCC, presenting promising avenues for the development of precision medicine strategies in clinical practice.

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来源期刊

Translational Oncology ONCOLOGY-

CiteScore

8.40

自引率

2.00%

发文量

314

审稿时长

54 days

期刊介绍： Translational Oncology publishes the results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of oncology patients. Translational Oncology will publish laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer. Peer reviewed manuscript types include Original Reports, Reviews and Editorials.