Su(var)3-9, Enhancer of Zeste, and Trithorax Domain-Containing 5 Facilitates Tumor Growth and Pulmonary Metastasis through Up-Regulation of AKT1 Signaling in Breast Cancer.

Several studies have confirmed the function of Su(var)3-9, Enhancer of zeste, and Trithorax (SET) domain-containing 5 (SETD5) in post-translational modifications of nonhistone proteins. Mutation of the SETD5 gene has been implicated in the progression of many human cancers, such as breast cancer (BC), but its functional role in BC progression is still unknown. The current article investigates the clinical significance and the functional role of SETD5 in BC. Our studies show that SETD5 expression in BC was related to poor clinical outcomes, including lymph node metastasis and advanced clinical stage. SETD5 expression positively correlated with tumor-associated macrophages. SETD5 was an independent predictor of poor overall survival in BC. Furthermore, these studies show that down-regulation of SETD5 significantly decreased BC cell proliferation, metastasis, and angiogenesis, and increased apoptosis of BC cells. The mechanistic analysis showed that SETD5 contributes BC progression by interacting with AKT1 pathway. Also, in vivo experiments show that blocking of SETD5 expression significantly inhibited tumor growth and pulmonary metastasis of BC cells. These findings indicate that SETD5 is a potential prognosis marker and facilitates tumor progression of BC.