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A disintegrin-like and metalloprotease with therombospondin type1 motif 8 (ADAMTS8) plays an important role in many malignancies. However, the clinical and biological significance of  ADAMTS8  in breast cancer remain unknown. In this study, the clinical data from 1066 breast cancer patients were analyzed by The Cancer Genome Atlas (TCGA) database, and were analyzed using the correlation between  ADAMTS8  expression and the clinicopathological features and prognoses. The CCK-8 assay, clone formation assay, flow cytometry and Transwell assay were used to characterize the effects of  ADAMTS8  on proliferation, migration and invasion of breast cancer cells. Gene set enrichment analysis (GSEA) and western blotting were used to identify the potential molecular mechanism on how  ADAMTS8  exert its biological function.  ADAMTS8  overexpression correlated longer overall survival (OS) and progression-free survival (PFS).  ADAMTS8  was considered as an independent prognostic factor for OS.  ADAMTS8  overexpression inhibited breast cancer cell proliferation, migration and invasion  in vitro , and induced G2/M cell cycle arrest.  ADAMTS8  was also involved in cell cycle regulation and was associated with the EGFR/Akt signaling pathway.  ADAMTS8  knockdown showed the reverse effect. Together, the results showed that  ADAMTS8  functioned as a tumor suppressor gene (TGS) and could be a prognostic biomarker for breast cancer.

The Prognostic Value of ADAMTS8 and Its Role as a Tumor Suppressor in Breast Cancer