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

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

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.

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.

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

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.