POTEE drives colorectal cancer development via regulating SPHK1/p65 signaling
POTEE drives colorectal cancer development via regulating SPHK1/p65 signaling
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POTEE 通过调节 SPHK1/p65 信号传导驱动结直肠癌的发展
DOI：
10.1038/s41419-019-2046-7
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发表时间：
2019-11-13
影响因子：
9
通讯作者：
Deng, Haijun
中科院分区：
文献类型：
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作者：
Shen, Zhiyong;Feng, Xiaochuang;Deng, Haijun
基因表达异常在结直肠癌的发生发展中起着重要作用。我们发现POTE锚蛋白家族成员POTEE在结直肠肿瘤中表达显著上调，并预测结直肠癌患者的总生存率。在CRC细胞中，POTEE可作为致癌基因，并可促进细胞生长、细胞周期进展、抑制细胞凋亡和提高异种移植肿瘤生长。在机制上，我们使用微阵列分析并鉴定了POTEE/SPHK 1/p65信号传导轴，其影响CRC细胞的生物学功能。进一步的研究表明，POTEE的过表达可以增加SPHK 1蛋白的表达，进而促进p65蛋白的磷酸化和活化。总之，我们的研究结果表明，POTEE/SPHK 1/p65信号轴可以促进结直肠肿瘤的发生，POTEE可能作为一种新的生物标志物，用于诊断和干预结直肠癌。
Aberrant gene expression plays critical roles in the development of colorectal cancer (CRC). Here we show that POTEE, which was identified as a member E of POTE ankyrin domain family, was significantly upregulated in colorectal tumors and predicted poor overall survival of CRC patients. In CRC cells, POTEE could act as an oncogene and could promote cell growth, cell-cycle progression, inhibit apoptosis, and elevates xenograft tumor growth. Mechanically, we used microarray analysis and identified a POTEE/SPHK1/p65 signaling axis, which affected the biological functions of CRC cells. Further evaluation showed that overexpression of POTEE could increase the protein expression of SPHK1, followed by promoting the phosphorylation and activation of p65 protein. Altogether, our findings suggested a POTEE/SPHK1/p65 signaling axis could promote colorectal tumorigenesis and POTEE might potentially serve as a novel biomarker for the diagnosis and an intervention of colorectal cancer.