Department of Anatomy and Key Laboratory of Experimental Teratology, Ministry of Education, Shandong University School of Medicine, 44 Wenhuaxilu, Jinan, Shandong 250012, PR China.
Biochem Biophys Res Commun. 2013 May 3;434(2):352-6. doi: 10.1016/j.bbrc.2013.03.077. Epub 2013 Apr 2.
Increased cell migration and invasion lead to cancer metastasis and are crucial to cancer prognosis. In this study, we explore whether FBXW7 plays any role in metastatic process. We show that depletion of FBXW7 induces epithelial-mesenchymal transition (EMT) in human colon cancer cells along with the increase in cell migration and invasion. Moreover, FBXW7 deficiency promotes the generation of colon cancer stem-like cells in tumor-sphere culture. mTOR inhibition by rapamycin suppresses FBXW7 loss-driven EMT, invasion and stemness. Our results define the FBXW7/mTOR axis as a novel EMT pathway that mediates cancer invasion.
细胞迁移和侵袭的增加导致癌症转移，这对癌症预后至关重要。在这项研究中，我们探讨了 FBXW7 是否在转移过程中发挥作用。我们发现，FBXW7 的耗竭会诱导人结肠癌细胞发生上皮-间充质转化（EMT），同时增加细胞迁移和侵袭。此外，FBXW7 缺失促进了肿瘤球培养中结肠癌细胞癌干细胞样特性的产生。雷帕霉素抑制 mTOR 可抑制 FBXW7 缺失驱动的 EMT、侵袭和干性。我们的结果定义了 FBXW7/mTOR 轴作为一种新的 EMT 途径，介导癌症侵袭。
