Abstract
Here, we found that ING5 overexpression resulted in a lower proliferation, reduced glucose metabolism, S arrest, decreased migration and invasion, apoptotic induction, fat accumulation, autophagy, senescence and mesenchymal-epithelial–transition of breast cancer cells. It also suppressed the tumor growth of breast cancer cells by inhibiting proliferation, inducing apoptosis and autophagy. ING5-mediated chemoresistance was positively linked to Akt and NF-κB activation, MRP1 and GST-π overexpression, and FBXW7 hypoexpression. ING5 expression was higher in breast cancer than normal tissue at both mRNA and protein levels. ING5 mRNA expression was positively correlated with relapse- and distant metastasis-free survival rates. Nuclear ING5 expression showed gradual decrease from breast normal tissue, fibroadenoma, adenomatosis, primary to metastatic cancers, while versa for cytoplasmic ING5. Nuclear ING5 expression was negatively correlated with distant metastasis and p53 hypoexpression, while cytoplasmic ING5 expression was positively correlated with tumor size and ER expression. These data suggested that up-regulated expression and nucleocytoplasmic translocation of ING5 protein were observed in breast cancer. The higher expression of nuclear ING5 was inversely linked to worse clinicopathological behaviors of breast cancer by in vivo and vitro reversing aggressive phenotypes. Therefore, it should be employed as a biomarker to indicate the tumorigenesis and aggressiveness of breast cancer, and as a potential target for gene therapy.
Highlights
Breast cancer is a leading cancer in women worldwide, and more common in developed countries
We found that Inhibitor of growth 5 (ING5) overexpression resulted in a lower proliferation, reduced glucose metabolism, S arrest, decreased migration and invasion, apoptotic induction, fat accumulation, autophagy, senescence and mesenchymal-epithelial– transition of breast cancer cells
Nuclear ING5 expression was negatively correlated with distant metastasis and p53 hypoexpression, while cytoplasmic ING5 expression was positively correlated with tumor size and ER expression
Summary
Breast cancer is a leading cancer in women worldwide, and more common in developed countries. It is more important to clarify the molecular mechanisms of breast cancer, and find out a potential target for early diagnosis and gene therapy. ING5 was reported to promote DNA repair, induce apoptosis and chromatin remodeling by forming histone acetyl transferase (HAT) complexes [3,4,5]. It might activate the cyclin-dependent kinase inhibitor p21/waf promoter to induce p21 expression, enhance p53 acetylation at Lys-382 and Lys-120, and physically interact with p300 and p53 [6]. Its down-regulation was found in head and neck squamous cell carcinoma (HNSCC) with missense mutations within www.impactjournals.com/oncotarget
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