Post-translational modifications directly control protein activity and, thus, they represent an important means to regulate the responses of cells to different stimuli. Protein SUMOylation has recently been recognised as one such modification, and it has been associated with various diseases, including different types of cancer. However, the precise way that changes in SUMOylation influence the tumorigenic properties of cells remains to be fully clarified. Here, we show that blocking the SUMO pathway by depleting SUMO1 and UBC9, or by exposure to ginkgolic acid C15:1 or 2-D08 (two different SUMOylation inhibitors), induces cell death, also inhibiting the invasiveness of tumour cells. Indeed, diminishing the formation of SUMO1 complexes induces autophagy-mediated cancer cell death through increasing the expression of Tribbles pseudokinase 3 (TRIB3). Moreover, we found that blocking the SUMO pathway inhibits tumour cell invasion by decreasing RAC1 SUMOylation. These findings shed new light on the mechanisms by which SUMO1 modifications regulate the survival, and the migratory and invasive capacity of tumour cells, potentially establishing the bases to develop novel anti-cancer treatments based on the inhibition of SUMOylation.

中文翻译：

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抑制SUMO1介导的SUMOylation诱导自噬介导的癌细胞死亡，并减少通过RAC1侵袭的肿瘤细胞。

翻译后修饰直接控制蛋白质的活性，因此，它们代表了调节细胞对不同刺激反应的重要手段。蛋白质SUMOylation最近被认为是这种修饰之一，并且它与多种疾病（包括不同类型的癌症）有关。然而，SUMOylation改变影响细胞致瘤特性的确切方法仍有待充分阐明。在这里，我们显示出通过消耗SUMO1和UBC9或暴露于银杏酸C15：1或2-D08（两种不同的SUMO酰化抑制剂）来阻断SUMO途径，可诱导细胞死亡，并抑制肿瘤细胞的侵袭性。确实，减少SUMO1复合物的形成可通过增加Tribbles假激酶3（TRIB3）的表达诱导自噬介导的癌细胞死亡。此外，我们发现阻断SUMO途径可通过降低RAC1 SUMOylation抑制肿瘤细胞的侵袭。这些发现为SUMO1修饰调节生存的机制以及肿瘤细胞的迁移和侵袭能力提供了新的思路，从而为建立基于SUMOylation抑制作用的新型抗癌治疗方法奠定了基础。