<scp>EPHB2</scp> Promotes the Progression of Oral Squamous Cell Carcinoma Cells Through the Activation of <scp>VPS4A</scp>‐Mediated Autophagy

Oral squamous cell carcinoma (OSCC) is a prevalent type of head and neck neoplasm distinguished by a high risk of metastasis and a poor prognosis. Nevertheless, the fundamental mechanisms of OSCC cell proliferation and metastasis remain poorly understood. Autophagy, as the principal intracellular degradation system, has been implicated in OSCC progression; however, its underlying mechanism remains unclear. In this study, transcriptomic sequencing analysis was performed using both The Cancer Genome Atlas (TCGA) database and samples from OSCC patients and revealed significant upregulation of EPHB2 expression, which is positively correlated with OSCC metastasis and a poor prognosis. In subsequent studies, we observed that the knockdown of EPHB2 resulted in the blockade of autophagic flux due to impaired lysosomal function, leading to inhibited proliferation, migration, and invasion in OSCC cells. Furthermore, the knockdown of EPHB2 significantly suppressed the expression of VPS4A, a key mediator that facilitates autolysosomal degradation. The overexpression of VPS4A restored lysosomal function and autophagic flux, thereby attenuating the inhibitory effects of EPHB2 knockdown on OSCC cell progression. The findings of this study demonstrate that the molecular mechanism underlying EPHB2 regulation of autophagic flux to promote OSCC progression is by regulating VPS4A activity and that EPHB2 may be a diagnostic biomarker and therapeutic target for OSCC prevention and treatment.