Integrin α5β1 in head and neck squamous cell carcinoma: expression, mechanisms, and clinical implications

Head and neck squamous cell carcinoma (HNSCC) represents a significant global health challenge associated with high mortality. A major obstacle in its management is therapeutic resistance, which limits the efficacy of existing treatment modalities. Altered expression of integrins, a family of cell adhesion receptors, has been shown to influence tumor proliferation, migration, and invasion. Among them, integrin α5β1, a member of the RGD (Arg-Gly-Asp)-recognizing integrin subfamily, has emerged as a potentially critical mediator of HNSCC progression and therapeutic resistance, according to a growing body of research. In this review, we assess the evidence regarding the aberrant expression of integrin α5β1 in HNSCC, with a particular focus on common subtypes such as oral squamous cell carcinoma (OSCC), nasopharyngeal carcinoma (NPC), and laryngeal squamous cell carcinoma (LSCC). We then summarize its potential value as a diagnostic and prognostic marker. Furthermore, we discuss the molecular mechanisms that regulate integrin α5β1 and its downstream signaling, especially in the context of therapy resistance. Finally, we outline the potential clinical applications and future research directions related to targeting integrin α5β1. Collectively, this paper aims to synthesize the current knowledge of integrin α5β1 in HNSCC, providing a foundation for the development of personalized, tumor-specific diagnostic tools and targeted therapies.