J Clin Invest. 2021 Aug 16;131(16). doi: 10.1172/JCI151295.
Phosphofructokinase 1 (PFK1) is expressed in T cell acute lymphoblastic leukemia (T-ALL), where its upregulation is linked with cancer progression. While PFK1 functions in the glycolysis pathway within the cytoplasm, it is also present in the nucleus where it regulates gene transcription. In this issue of the JCI, Xueliang Gao, Shenghui Qin, et al. focus their mechanism-based investigation on the nucleocytoplasmic shuttling aspect of the PFK1 platelet isoform, PFKP. Functional nuclear export and localization sequences stimulated CXC chemokine receptor type 4 (CXCR4) expression to promote T-ALL invasion that involved cyclin D3/CDK6, c-Myc, and importin-9. Since the presence of nuclear PFKP is associated with poor survival in T-ALL, nuclear PFKP-induced CXCR4 expression might serve as a prognostic marker for T-ALL. More promising, though, are the mechanistic insights suggesting that approaches to dampening metastatic migration may have application to benefit patients with T-ALL.
磷酸果糖激酶 1（PFK1）在 T 细胞急性淋巴细胞白血病（T-ALL）中表达，其上调与癌症进展有关。虽然 PFK1 在细胞质中的糖酵解途径中发挥作用，但它也存在于细胞核中，在细胞核中它调节基因转录。在本期 JCI 中，高雪亮、秦生辉等将他们的基于机制的研究重点放在 PFK1 血小板同工型 PFKP 的核质穿梭方面。功能性核输出和定位序列刺激 CXC 趋化因子受体 4（CXCR4）的表达，促进 T-ALL 浸润，涉及周期蛋白 D3/CDK6、c-Myc 和 importin-9。由于核 PFKP 的存在与 T-ALL 的生存不良相关，因此核 PFKP 诱导的 CXCR4 表达可能成为 T-ALL 的预后标志物。不过，更有希望的是，这些机制研究为抑制转移性迁移的方法提供了应用于 T-ALL 患者的潜力。
