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.

中文翻译：

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SUMO活化酶在癌症干细胞维持和自我更新中的作用。

癌症干细胞（CSC）在抗药性，肿瘤转移和复发中起关键作用。我们使用结直肠癌（CC）细胞系，患者来源的异种移植（PDX）组织和患者组织，在这里我们报告说，抗化学辐射的CC CSC比非CSC具有更高的SUMO活化酶（E1）和整体SUMOylation水平。抑制SUMO E1或SUMO共轭酶（E2）抑制CC CSC的维持和自我更新，而SUMO E1或E2的过表达增加CC细胞的干性。我们发现SUMOylation通过Oct-1（醛脱氢酶（ALDHs）的转录因子）调节CSC。ALDH活性不仅是CSC的标志物，而且在CSC生物学中也很重要。SUMO不会直接修饰Oct-1，而是调节TRIM21的表达，从而增强Oct-1泛素化，从而降低Oct-1的稳定性。