Downregulation of nuclear ING3 expression and translocalization to cytoplasm promotes tumorigenesis and progression in head and neck squamous cell carcinoma (HNSCC)

Abstract

ING3 (inhibitor of growth gene 3) is a member of the ING gene family, and is considered as a candidate tumor suppressor gene. In order to explore the roles of ING3 in tumorigenesis and cancer progression of head and neck squamous cell carcinoma (HNSCC), ING3 expression was assessed in 173 cases of HNSCC by immunohistochemistry. The expression of ING3 was also compared to clinicopathological variables, and the expression of several tumorigenic markers. Nuclear expression of ING3 in HNSCC was significantly lower than that in dysplasia and normal epithelium, and was negatively correlated with a poor-differentiated status, T staging and TNM staging. In contrast, cytoplasmic expression of ING3 was significantly increased in HNSCC, and was statistically associated with lymph node metastasis and 14-3-3η expression. In addition, nuclear expression of ING3 was positively correlated with the expression of p300, p21 and acetylated p53. In conclusion, decreases in nuclear ING3 may play important roles in tumorigenesis, progression and tumor differentiation in HNSCC. Increases in cytoplasmic ING3 may be due to 14-3-3η binding and may also be involved in malignant progression. Nuclear ING3 may modulate the transactivation of target genes, promoting apoptosis through interactions with p300 and p21. Moreover, ING3 may interact with p300 to upregulate the level of acetylation of p53, and promote p53-mediated cell cycle arrest, senescence and/or apoptosis. Therefore, ING3 may be a potential tumor suppressor and a possible therapeutic target in HNSCC.