The histone H3K9 methyltransferase SETDB2 is involved in cell cycle dysregulation in acute leukemia and has oncogenic roles in gastric cancer. In our study, we found that SETDB2 plays essential roles in breast cancer stem cell maintenance. Depleted SETDB2 significantly decreased the breast cancer stem cell population and mammosphere formation in vitro and also inhibited breast tumor initiation and growth in vivo. Restoring SETDB2 expression rescued the defect in breast cancer stem cell maintenance. A mechanistic analysis showed that SETDB2 upregulated the transcription of the ΔNp63α downstream Hedgehog pathway gene. SETDB2 also interacted with and methylated ΔNp63α, and stabilized ΔNp63α protein. Restoring ΔNp63α expression rescued the breast cancer stem cell maintenance defect which mediated by SETDB2 knockdown. In conclusion, our study reveals a novel function of SETDB2 in cancer stem cell maintenance in breast cancer.

中文翻译：

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SETDB2 通过与 ΔNp63α 蛋白的相互作用和稳定来促进乳腺癌干细胞的维持。

组蛋白 H3K9 甲基转移酶 SETDB2 参与急性白血病的细胞周期失调，并在胃癌中具有致癌作用。在我们的研究中，我们发现 SETDB2 在乳腺癌干细胞维持中起着至关重要的作用。耗尽的 SETDB2 在体外显着减少了乳腺癌干细胞群和乳腺球的形成，并在体内抑制了乳腺肿瘤的发生和生长。恢复 SETDB2 表达挽救了乳腺癌干细胞维持的缺陷。机制分析表明，SETDB2 上调了 ΔNp63α 下游 Hedgehog 通路基因的转录。SETDB2 还与 ΔNp63α 相互作用并甲基化，并稳定 ΔNp63α 蛋白。恢复 ΔNp63α 表达挽救了由 SETDB2 敲低介导的乳腺癌干细胞维持缺陷。综上所述，