S100A10 promotes tumorigenesis and metastasis in lung adenocarcinoma by regulating JUND/TNC axis-mediated EMT

BACKGROUND: Recurrence and metastasis significantly impact the prognosis of lung adenocarcinoma (LUAD), yet effective therapies targeting these processes remain limited, especially in advanced stages. This study investigates the role of S100A10 as an oncogenic driver in LUAD progression via epithelial-mesenchymal transition (EMT). METHODS: S100A10 expression was analyzed in public datasets and correlated with patient survival. Functional studies involved S100A10 knockdown or overexpression in LUAD cell lines, assessing viability (CCK-8), migration, invasion (Transwell, wound healing), mRNA (qPCR), and protein (Western blot). Tumorigenicity was evaluated using in vivo models. A small-molecule inhibitor, [D-Leu-4]-OB3, was identified through virtual screening and tested for its effect on S100A10 and LUAD. RESULTS: High S100A10 expression correlated with poor outcomes in LUAD. Knockdown of S100A10 suppressed cell viability, migration, invasion, and EMT both in vitro and in vivo, while overexpression enhanced these malignant traits. Mechanistically, S100A10 activated JUND and Tenascin-C (TNC), promoting EMT. Re-expression of TNC rescued the anti-metastatic effects of S100A10 inhibition. [D-Leu-4]-OB3 specifically targeted S100A10, inhibiting LUAD growth and metastasis. CONCLUSION: S100A10 promotes LUAD progression and metastasis through JUND/TNC-mediated EMT. [D-Leu-4]-OB3 represents a promising targeted therapy for LUAD by inhibiting S100A10.