Department of Surgery, Huashan Hospital, Fudan University, Shanghai 200032, PR China.
Oncol Rep. 2012 Dec;28(6):2029-34. doi: 10.3892/or.2012.2025. Epub 2012 Sep 12.
The cellular prion protein (PrPc) is a glycoprotein anchored by glycosylphosphatidylinositol to the cell surface and is abundantly expressed in various tissues. The putative roles of PrPc are thought to be related to cell signaling, survival, and differentiation and cancer progression. In this study, we demonstrated that the expression of PrPc correlates with a more aggressive and histologically unfavorable disease in colorectal carcinomas. Moreover, we found that PrPc mediates the process of epithelial-mesenchymal transition and, thereby, promotes CRC metastasis. Transcriptome profiling of PrPc-depleted cells revealed downregulation of the special AT-rich sequence-binding protein-1 (SATB1). PrPc is demonstrated to be involved in regulating SATB1 expression via the Fyn-SP1 pathway. Since SATB1 has been previously proposed as a key protein that controls tumor development and progression, knockdown of PrPc resulted in a reduced metastatic capacity in CRC cells, as well as a reduction in distant metastases in vivo. In conclusion, our data characterize a novel molecular mechanism that links PrPc expression to the regulation of CRC metastasis. Targeting PrPc will, therefore, be a promising strategy to overcome the metastatic advantage in colorectal tumors.
细胞朊蛋白（PrPc）是一种糖基磷脂酰肌醇锚定的糖蛋白，在各种组织中大量表达。PrPc 的假定作用被认为与细胞信号转导、存活和分化以及癌症进展有关。在这项研究中，我们证明了 PrPc 的表达与结直肠癌中更具侵袭性和组织学不良的疾病相关。此外，我们发现 PrPc 介导上皮-间充质转化过程，从而促进 CRC 转移。PrPc 耗尽细胞的转录组谱分析显示，特殊 AT 富含序列结合蛋白 1（SATB1）下调。PrPc 通过 Fyn-SP1 途径被证明参与调节 SATB1 的表达。由于 SATB1 先前被提议作为控制肿瘤发生和进展的关键蛋白，因此 PrPc 的敲低导致 CRC 细胞的转移能力降低，体内远处转移减少。总之，我们的数据描述了一种将 PrPc 表达与 CRC 转移调节联系起来的新分子机制。因此，靶向 PrPc 将是克服结直肠肿瘤转移优势的有前途的策略。
