Role of SUMO activating enzyme in cancer stem cell maintenance and self-renewal.
Role of SUMO activating enzyme in cancer stem cell maintenance and self-renewal.
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DOI：
10.1038/ncomms12326
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发表时间：
2016-07-28
影响因子：
16.6
通讯作者：
Chen Y
中科院分区：
文献类型：
--
作者：
Du L;Li YJ;Fakih M;Wiatrek RL;Duldulao M;Chen Z;Chu P;Garcia-Aguilar J;Chen Y
癌症干细胞（CSCs）在治疗抵抗、肿瘤转移和复发中具有关键作用。使用结直肠癌（CC）细胞系，患者来源的异种移植物（PDX）组织和患者组织，在这里，我们报告说，CC CSC，抵抗放化疗，具有较高的SUMO激活酶（E1）和全球SUMO化水平比非CSC。SUMO E1或SUMO结合酶（E2）的敲低抑制CC CSC的维持和自我更新，而SUMO E1或E2的过表达增加CC细胞的干细胞性。我们发现SUMO化通过Oct-1调节CSC，Oct-1是乙醛脱氢酶（ALDH）的转录因子。ALDH活性不仅是CSC的标志物，而且在CSC生物学中也是重要的。SUMO不直接修饰Oct-1，但调节TRIM 21的表达，TRIM 21增强Oct-1泛素化，从而降低Oct-1的稳定性。总之，我们的研究结果表明，SUMO化可能是抑制CSC并最终减少治疗抵抗、肿瘤转移和复发的靶点。 肿瘤干细胞（CSCs）在肿瘤的发生和转移中起着关键作用。在这里，作者表明结直肠CSC中SUMO E1和整体sumoylation水平很高，并且SUMO E1催化亚基SAE 2的耗尽通过TRIM 21介导的Oct 1（ALDH的转录因子）降解来影响CSC的自我更新。
Cancer stem cells (CSCs) have key roles in treatment resistance, tumour metastasis and relapse. Using colorectal cancer (CC) cell lines, patient-derived xenograft (PDX) tissues and patient tissues, here we report that CC CSCs, which resist chemoradiation, have higher SUMO activating enzyme (E1) and global SUMOylation levels than non-CSCs. Knockdown of SUMO E1 or SUMO conjugating enzyme (E2) inhibits CC CSC maintenance and self-renewal, while overexpression of SUMO E1 or E2 increases CC cell stemness. We found that SUMOylation regulates CSCs through Oct-1, a transcription factor for aldehyde dehydrogenases (ALDHs). ALDH activity is not only a marker for CSCs but also important in CSC biology. SUMO does not modify Oct-1 directly, but regulates the expression of TRIM21 that enhances Oct-1 ubiquitination and, consequently, reducing Oct-1 stability. In summary, our findings suggest that SUMOylation could be a target to inhibit CSCs and ultimately to reduce treatment resistance, tumour metastasis and relapse. Cancer stem cells (CSCs) have key roles in tumor initiation and metastasis. Here, the authors show that the SUMO E1 and global sumoylation levels are high in colorectal CSCs and that depletion of the catalytic subunit of the SUMO E1, SAE2, affects CSCs self-renewal through TRIM21-mediated degradation of the Oct1, a transcription factor for ALDH.