The deubiquitinase USP54 is overexpressed in colorectal cancer stem cells and promotes intestinal tumorigenesis.
The deubiquitinase USP54 is overexpressed in colorectal cancer stem cells and promotes intestinal tumorigenesis.
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DOI：
10.18632/oncotarget.12769
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发表时间：
2016-11-15
期刊：
影响因子：
--
通讯作者：
Freije JM
中科院分区：
文献类型：
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作者：
Fraile JM;Campos-Iglesias D;Rodríguez F;Español Y;Freije JM
泛素特异性蛋白酶（USP）是在人类恶性肿瘤中经常失调的去泛素化酶。在这里，我们发现USP54在肠干细胞中过表达，并证明其在结直肠癌细胞中的下调阻碍了肿瘤的发生。我们已经产生了这种去泛素化酶缺陷的突变小鼠，它们是可行的和可繁殖的，并保护免受化学诱导的结直肠癌。此外，我们发现USP54在人类结肠癌中上调，并与预后不良相关。与这些结果一致，小鼠黑素瘤细胞中的Usp54下调抑制肺转移形成。总的来说，这项工作揭示了USP54的促肿瘤发生特性，突出了去泛素化酶作为开发特定抗癌疗法的有希望靶点的重要性。
Ubiquitin-Specific Proteases (USPs) are deubiquitinating enzymes frequently deregulated in human malignancies. Here, we show that USP54 is overexpressed in intestinal stem cells and demonstrate that its downregulation in colorectal carcinoma cells impedes tumorigenesis. We have generated mutant mice deficient for this deubiquitinase, which are viable and fertile, and protected against chemically-induced colorectal carcinoma. Furthermore, we show that USP54 is upregulated in human colon cancer and associates with poor prognosis. In agreement with these results, Usp54 downregulation in mouse melanoma cells inhibits lung metastasis formation. Collectively, this work has uncovered the pro-tumorigenic properties of USP54, highlighting the importance of deubiquitinating enzymes as promising targets for the development of specific anti-cancer therapies.