Periostin Promotes Invasiveness and Metastasis of Oral Cancer via Epithelial-mesenchymal Transition

Oral squamous cell carcinoma (OSCC) is a significant global health burden, with a modest 5-year survival rate; therefore, novel therapeutic targets are needed. Periostin, an extracellular matrix protein, is implicated in tumor progression, yet its role in OSCC, particularly via epithelial-mesenchymal transition (EMT), is poorly understood.

We investigated periostin's role in OSCC using a multifaceted approach: retrospective analysis of 97 OSCC patient samples, bioinformatics analyses of GEO and TCGA datasets, and in vitro/in vivo experiments using the HNSCC-31 cell line and xenograft mouse models. Periostin expression was assessed via immunohistochemistry and western blotting. Functional effects were evaluated through cell viability, colony formation, migration, invasion, and EMT marker expression assays following periostin over-expression (Ad-POSTN), knockdown (Lenti-shPOSTN) or recombinant periostin treatment.

Periostin expression was significantly elevated in OSCC tissue compared than normal tissue (p<0.001) and correlated with lymph node metastasis (p=0.011), higher AJCC stage (p=0.008), and recurrence (p=0.001). High periostin levels independently predicted poor disease-free [hazard ratio (HR)=2.329, p=0.019] and overall survival (HR=2.842, p=0.009). In vitro, periostin up-regulation enhanced viability, colony formation, migration, and invasion, and EMT (increased vimentin, Snail, MMP-9, N-cadherin; decreased E-cadherin), while knockdown reversed these effects. In vivo, Ad-POSTN xenografts were significantly larger (p<0.05) and heavier (p<0.05) and showed increased periostin expression histologically.

Periostin promotes OSCC progression by enhancing invasiveness and metastasis via EMT. It represents a potential prognostic marker and therapeutic target. These findings highlight the need for further clinical validation of periostin-targeted therapies for management of OSCC.