Purpose: Zinc finger protein 259 (ZNF259), also known as ZPR1, is a zinc finger-containing protein that can bind the intracellular tyrosine kinase domain of EGFR. At present, our knowledge on ZNF259 in cancers is limited. Here, we aimed to explore the biological functions of ZNF259 in breast cancer and reveal their mechanisms.
Patients and methods: The expression of ZNF259 was measured in 133 cases of breast cancer by immunohistochemistry. The online database Kaplan–Meier (KM) Plotter Online Tool was used to analyze the relationship between ZNF259 expression and breast cancer patient survival prognosis. Plasmid transfection and small interfering RNA and inhibitor treatments were carried out to explore the functions of ZNF259 in breast cancer cell lines and its potential mechanism. Matrigel invasion and wound healing assays were performed to detect the invasion and migration ability of cancer cells. In addition, protein expressions in tissues and cells were determined by Western blotting.
Results: ZNF259 expression was much higher in breast cancer cells than in the adjacent normal breast duct glandular epithelial cells (75.94% vs 7.52%, P <0.001) and was closely related to the breast cancer patients’ TNM stages (P =0.013) and lymph node metastasis (P =0.021). Knockdown of ZNF259 could downregulate p-ERK, p-GSK3β, and Snail expression, and upregulate the expression of E-cadherin and ZO-1, and then it also inhibited invasion and migration by the breast cancer cell lines MCF-7 and MDA-MB-231. Correspondingly, ZNF259 transfection could upregulate p-ERK, p-GSK3β, and Snail expression, and downregulate E-cadherin and ZO-1 expression, which led to stronger invasion and migration abilities of cancer cells. Furthermore, the ERK inhibitor U0126 could reverse all these effects induced by ZNF259 transfection.
Conclusion: ZNF259 could promote breast cancer cell invasion and migration by activating the ERK/GSK3β/Snail signaling pathway.
Keywords: ZPR1, E-cadherin, ZO-1, U0126, p-ERK, p-GSK3β