SPON2 acts as a tumor promoter in HR-positive/HER2-negative breast cancer by regulating β-catenin signaling.

Background: Spondin-2 (SPON2) expression is associated with various types of cancer, but its role in breast cancer (BC) remains ambiguous, especially in hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) BC.

Methods: The expression of SPON2 in HR+/HER2- BC tissues and adjacent tissues was detected using immunohistochemical staining and western blotting. Cell proliferation and migration were assessed via CCK-8 assay, EdU assay, and transwell assay. Animal studies were performed to assess the effect of SPON2 knockdown on tumor growth.

Results: Herein, increased expression of SPON2 was found in HR+/HER2- BC, and silencing SPON2 suppressed cell proliferation, clonogenicity, and migration, whereas SPON2 overexpression had the opposite effects. Notably, SPON2 knockdown significantly suppressed tumor growth in a xenograft tumor assay. Mechanistically, a reduction in SPON2 expression inhibited β-catenin activation, whereas its overexpression promoted β-catenin-mediated proliferation and migration.

Conclusion: These data indicate that SPON2 plays oncogenic roles in HR+/HER2- BC via activating the β-catenin pathway, and may represent a potential therapeutic target for patients diagnosed with HR+/HER2- BC.