Oncol Res. 2017 Sep 21;25(8):1261-1267. doi: 10.3727/096504017X14871164924588. Epub 2017 Mar 2.
Forkhead box K1 (FOXK1) is a member of the FOX transcription factor family and plays an important role in the development of several tumors. However, the role of FOXK1 in the progression of prostate cancer remains unknown. Thus, the objectives of this study were to detect the expression of FOXK1 in prostate cancer and to examine its role in prostate cancer cells. We found that the expression of FOXK1 at both the mRNA and protein levels was significantly upregulated in human prostate cancer cell lines. In addition, the downregulation of FOXK1 obviously inhibited the cell proliferation of prostate cancer cells in vitro and attenuated tumor growth in a xenograft model in vivo. Furthermore, knockdown of FOXK1 suppressed the migration and invasion of prostate cancer cells, and prevented the EMT phenotype through upregulating the expression of E-cadherin, as well as downregulating the expression of N-cadherin in prostate cancer cells. Mechanistically, knockdown of FOXK1 efficiently downregulated the expression levels of β-catenin, c-myc, and cyclin D1 in PC-3 cells. Overall, our results demonstrated that knockdown of FOXK1 inhibited the proliferation and metastasis of prostate cancer, at least in part, through suppressing the Wnt/β-catenin signaling pathway. Therefore, these results suggest that FOXK1 may be a potential therapeutic target for human prostate cancer.
叉头框转录因子 K1(FOXK1)是 FOX 转录因子家族的成员,在几种肿瘤的发生发展中发挥着重要作用。然而,FOXK1 在前列腺癌进展中的作用尚不清楚。因此,本研究旨在检测 FOXK1 在前列腺癌细胞中的表达,并探讨其在前列腺癌细胞中的作用。我们发现,FOXK1 在 mRNA 和蛋白水平的表达在人前列腺癌细胞系中均显著上调。此外,FOXK1 的下调明显抑制了前列腺癌细胞在体外的增殖,并减弱了体内异种移植模型中的肿瘤生长。此外,下调 FOXK1 通过上调 E-钙黏蛋白的表达以及下调 N-钙黏蛋白的表达,抑制了前列腺癌细胞的迁移和侵袭,并阻止了 EMT 表型的发生。在机制上,FOXK1 的下调可有效下调 PC-3 细胞中β-连环蛋白、c-myc 和细胞周期蛋白 D1 的表达水平。总之,我们的研究结果表明,下调 FOXK1 可通过抑制 Wnt/β-连环蛋白信号通路抑制前列腺癌细胞的增殖和转移。因此,这些结果提示 FOXK1 可能是人类前列腺癌的一个潜在治疗靶点。