RUFY3 interaction with FOXK1 promotes invasion and metastasis in colorectal cancer.
RUFY3 interaction with FOXK1 promotes invasion and metastasis in colorectal cancer.
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RUFY3与FOXK1的相互作用促进结直肠癌的侵袭和转移
DOI：
10.1038/s41598-017-04011-1
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发表时间：
2017-06-16
影响因子：
4.6
通讯作者：
Wang J
中科院分区：
文献类型：
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作者：
Xie R;Wang J;Liu X;Wu L;Zhang H;Tang W;Li Y;Xiang L;Peng Y;Huang X;Bai Y;Liu G;Li A;Wang Y;Chen Y;Ren Y;Li G;Gong W;Liu S;Wang J
RUFY3在脑组织中高表达，并在神经元发育中发挥作用。转录因子FOXK1参与细胞生长和代谢。我们知道RUFY3或FOXK1与肿瘤细胞的恶性程度有关。然而，这些分子在结直肠癌(CRC)进展中的作用仍不清楚。用免疫印迹、免疫荧光和免疫组织化学方法检测其蛋白表达水平。用shRNA介导的体外和体内抑制法检测大肠癌细胞的迁移和侵袭能力。我们发现RUFY3在结直肠癌中的表达比在正常人结肠细胞系(FHC)中的表达上调。RUFY3抑制抑制了锚定非依赖性细胞肿瘤的发生。RUFY3诱导8种主要癌基因表达上调。此外，RUFY3在CRC中与FOXK1在物理上相互作用。RUFY3和FOXK1的表达模式呈正相关。此外，RUFY3和FOXK1的表达与肿瘤进展相关，并代表着结直肠癌患者总体生存的显著预测因子。SiRNA介导的FOXK1在RUFY3过表达细胞中的抑制逆转了上皮-间充质转化(EMT)和转移表型。在体内，FOXK1通过原位移植促进RUFY3介导的转移。这些发现提示RUFY3-FOXK1轴可能促进人类结直肠癌的发生发展。
RUFY3 is highly expressed in brain tissue and has a role in neuronal development. Transcriptional factor FOXK1 is involved in cell growth and metabolism. We knew that RUFY3 or FOXK1 has been correlated with the malignant of tumor cells. However, the role of these molecules in colorectal cancer (CRC) progression remains unknown. We investigated the protein expression levels by Western blot, immunofluorescence and immunohistochemistry analyses. The migration and invasive abilities of CRC cells were assessed using shRNA-mediated inhibition in vitro and in vivo. We showed that RUFY3 expression was up-regulated in CRC compared with its expression in a normal human colon cell line (FHC). RUFY3 suppression inhibited anchorage independent cell tumorigenesis. RUFY3 induced elevated expression of eight major oncogenes. Moreover, RUFY3 physically interacts with FOXK1 in CRC. A positive correlation was observed between the expression patterns of RUFY3 and FOXK1. Furthermore, RUFY3 and FOXK1 expression were correlated with tumor progression and represented significant predictors of overall survival in CRC patients. SiRNA-mediated repression of FOXK1 in RUFY3-overexpressing cells reversed the epithelial-mesenchymal transition (EMT) and metastatic phenotypes. In vivo, FOXK1 promoted RUFY3-mediated metastasis via orthotopic implantation. These findings suggest that the RUFY3-FOXK1 axis might promote the development and progression of human CRC.