MYC-nick promotes cell migration by inducing fascin expression and Cdc42 activation
MYC-nick promotes cell migration by inducing fascin expression and Cdc42 activation
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DOI：
10.1073/pnas.1610994113
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发表时间：
2016-09-13
影响因子：
11.1
通讯作者：
Conacci-Sorrell, Maralice
中科院分区：
文献类型：
--
作者：
Anderson, Sarah;Poudel, Kumud Raj;Conacci-Sorrell, Maralice
MYC-NICK是MYC癌蛋白家族中转录不活跃的细胞质成员，由全长MYC的蛋白水解酶产生。MYC-NICK促进细胞的迁移和存活，以应对化疗药物或停用葡萄糖。在这里，我们报告了MYC-NICK在来自WNT、转化生长因子-β和PI3K通路突变的小鼠模型的结肠和肠道肿瘤中的丰富表达。此外，在缺失FBWX7的结肠癌细胞中，MYC-NICK水平升高，FBWX7编码在结直肠癌中频繁突变的全长MYC的主要E3连接酶。MYC-NICK促进在3D培养中检测的或在斑马鱼转移模型中作为异种移植生长的结肠癌细胞的迁移。MYC-NICK通过激活Rho GTP酶CDC42和诱导Fasin表达来加速迁移。在人类大肠肿瘤侵袭前沿的细胞中，MYC-NICK、Fascin和CDC42的表达经常上调，这表明这些蛋白在肿瘤迁移中具有协同作用。
MYC-nick is a cytoplasmic, transcriptionally inactive member of the MYC oncoprotein family, generated by a proteolytic cleavage of full-length MYC. MYC-nick promotes migration and survival of cells in response to chemotherapeutic agents or withdrawal of glucose. Here we report that MYC-nick is abundant in colonic and intestinal tumors derived from mouse models with mutations in the Wnt, TGF-beta, and PI3K pathways. Moreover, MYC-nick is elevated in colon cancer cells deleted for FBWX7, which encodes the major E3 ligase of full-length MYC frequently mutated in colorectal cancers. MYC-nick promotes the migration of colon cancer cells assayed in 3D cultures or grown as xenografts in a zebrafish metastasis model. MYC-nick accelerates migration by activating the Rho GTPase Cdc42 and inducing fascin expression. MYC-nick, fascin, and Cdc42 are frequently up-regulated in cells present at the invasive front of human colorectal tumors, suggesting a coordinated role for these proteins in tumor migration.