异常细胞增殖是癌症（包括乳腺癌）的标志。在这里，我们证明 USP27X 是乳腺癌细胞增殖和肿瘤发生所必需的。我们鉴定了 MYC 信号轴的 PIM2-USP27X 调节因子，其活性对乳腺癌的肿瘤生物学有重要贡献。 PIM2 磷酸化 USP27X，并促进其对 MYC 的去泛素化活性，从而促进其蛋白质稳定性并导致乳腺癌中 HK2 介导的有氧糖酵解增加。此外，PIM2-USP27X-MYC 轴也在 PIM2 敲除小鼠中得到验证。总而言之，这些发现表明 PIM2-USP27X-MYC 信号轴是乳腺癌治疗的新潜在靶标。© 2024。作者，获得 Springer Nature Limited 的独家许可。

Aberrant cell proliferation is a hallmark of cancer, including breast cancer. Here, we show that USP27X is required for cell proliferation and tumorigenesis in breast cancer. We identify a PIM2-USP27X regulator of MYC signaling axis whose activity is an important contributor to the tumor biology of breast cancer. PIM2 phosphorylates USP27X, and promotes its deubiquitylation activity for MYC, which promotes its protein stability and leads to increase HK2-mediated aerobic glycolysis in breast cancer. Moreover, the PIM2-USP27X-MYC axis is also validated in PIM2-knockout mice. Taken together, these findings show a PIM2-USP27X-MYC signaling axis as a new potential target for breast cancer treatment.© 2024. The Author(s), under exclusive licence to Springer Nature Limited.