Background: Breast cancer (BCa) has been the most commonly diagnosed cancer worldwide and the leading cause of cancer-related death. Dual-specificity phosphatase 28 (DUSP28) is associated with various cancer progression, but its function and mechanism in breast cancer remain unclear.
Methods: DUSP28 level was identified by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot assays. The proliferation, migration, and invasion of DUSP28 in MCF-7 and MDA-MB-231 cells were assessed by Cell Counting kit-8 (CCK-8), colony formation, and transwell assays. The xenograft tumor model was established to explore the effects of DUSP28 on tumor growth of nude mice. Immunohistochemistry (IHC) and western blot assays were performed to evaluate the expression of related signal molecules.
Results: The expression of DUSP28 was up-regulated in BCa tissues and closely correlated with tumor size and distant lymphatic metastasis in The Cancer Genome Atlas (TCGA) dataset. Quantitative real-time PCR and western blot assays indicated that the expression of DUSP28 was up-regulated in BCa cells. DUSP28 was demonstrated to promote the proliferation, migration, and invasion of MCF-7 and MDA-MB-231 cells in vitro. Knockdown of DUSP28 inhibited tumor growth of xenograft tumor mice in vivo and reduced the levels of DUSP28 and Ki-67. Notably, further mechanism analysis indicated that DUSP28 promoted the activation of Akt/β-catenin/Slug signaling.
Conclusion: DUSP28 exerts its oncogene function via regulating Akt/β-catenin/Slug signaling in BCa, indicating that DUSP28 may provide a promising therapeutic target for the treatment of BCa.