Department of Pathology, Xuzhou Medical University, Xuzhou, China.
Department of Pathology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
J Cell Mol Med. 2020 Jun;24(11):6308-6323. doi: 10.1111/jcmm.15272. Epub 2020 Apr 19.
Finding out the driver gene critical for the maintenance of breast cancer stem cells (BrCSCs) is important for designing a new strategy to eradicate these cells to improve patient's prognosis. Here, in our study, we revealed that PIM1, an oncogenic serine-threonine kinase and a well-proven contributor to the tumorigenesis of breast cancer, was involved in BrCSCs regulation and promised to be a new target for eradicating BrCSCs. In brief, PIM1 could enhance the stem cell-like traits of breast cancer cells by promoting the phosphorylation and cytoplasmic localization of RUNX3. The nuclear dislocation of RUNX3 disabled this tumour suppressor and led to breast cancer cells gaining stem cell-like traits. Inhibition of PIM1 significantly induced the nuclear retention of RUNX3, recovered its transcriptional function and attenuated the stem cell-like properties of breast cancer cells. Those findings deepened our understanding of PIM1's oncogenic effect, underlining the significance of PIM1 in designing a new strategy aimed at BrCSCs.
寻找维持乳腺癌干细胞（BrCSCs）的关键驱动基因对于设计一种新的策略来根除这些细胞以改善患者预后非常重要。在这里，我们的研究揭示了 PIM1，一种致癌丝氨酸-苏氨酸激酶，也是乳腺癌发生的一个公认的贡献者，参与了 BrCSCs 的调节，并有望成为根除 BrCSCs 的新靶点。简而言之，PIM1 可以通过促进 RUNX3 的磷酸化和细胞质定位来增强乳腺癌细胞的干细胞样特征。RUNX3 的核易位使这个肿瘤抑制因子失活，导致乳腺癌细胞获得干细胞样特征。PIM1 的抑制显著诱导 RUNX3 的核保留，恢复其转录功能，并减弱乳腺癌细胞的干细胞样特性。这些发现加深了我们对 PIM1 致癌作用的理解，强调了 PIM1 在设计旨在针对 BrCSCs 的新策略中的重要性。
