FOXK1 promotes malignant progression of breast cancer by activating PI3K/AKT/mTOR signaling pathway.

Abstract

The aim of this study was to investigate the expression characteristics of forkhead box K1 (FOXK1) in breast cancer (BCa). Meanwhile, its relationship with clinicopathology and prognosis of patients with BCa was also explored. The expression level of FOXK1 in 65 paired BCa tissues and para-cancerous tissues was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The relationship between FOXK1 expression and BCa pathological parameters as well as the prognosis of patients was analyzed. Meanwhile, the expression of FOXK1 in BCa cells was detected by qRT-PCR. Subsequently, FOXK1 knockdown and overexpression models were constructed by lentivirus transfection in BCa cell lines (including MCF-7 and SKBR3). The effect of FOXK1 on the biological functions of BCa cells was analyzed using Cell Counting Kit-8 (CCK-8), cell cloning assay and flow cytometry, respectively. Finally, whether the role of FOXK1 was achieved via the PI3K/AKT/mTOR signaling pathway was explored. The qRT-PCR results showed that FOXK1 expression in BCa tissues was significantly higher than that of adjacent tissues. Compared with patients with low expression of FOXK1, the pathological grading was markedly higher in those with high expression. Meanwhile, the overall survival rate was remarkably lower in patients with high expression. In addition, compared with the negative control group, the proliferation ability of cells in FOXK1 knockdown group was significantly decreased, while cell apoptosis was markedly up-regulated. Besides, Western blot results revealed that silencing FOXK1 could reduce the levels of key proteins in the PI3K/AKT/mTOR signaling pathway, thereby promoting the malignant progression of BCa. Finally, PI3Kα/mTOR-IN-1, which was the inhibitor of the PI3K/AKT/mTOR signaling pathway, significantly reversed the proliferative capacity of cells in FOXK1 overexpression group, as well as enhanced anti-apoptotic ability. FOXK1 expression was remarkably increased both in BCa tissues and cells. Meanwhile, it was markedly associated with pathological stage and poor prognosis of patients. Besides, FOXK1 might promote the malignant progression of BCa by inhibiting the PI3K/AKT/mTOR signaling pathway.