Cell Signaling and Cancer Laboratory, Leeds Institute of Cancer and Pathology, Faculty of Medicine and Health, University of Leeds, St James' University Hospital, Beckett Street, Leeds, UK.
Department of Research & Development, hVIVO PLC, Biopark, Broadwater Road, Welwyn Garden City, UK.
Oncogene. 2019 Mar;38(13):2223-2240. doi: 10.1038/s41388-018-0582-8. Epub 2018 Nov 28.
Most tumor cells reprogram their glucose metabolism as a result of mutations in oncogenes and tumor suppressors, leading to the constitutive activation of signaling pathways involved in cell growth. This metabolic reprogramming, known as aerobic glycolysis or the Warburg effect, allows tumor cells to sustain their fast proliferation and evade apoptosis. Interfering with oncogenic signaling pathways that regulate the Warburg effect in cancer cells has therefore become an attractive anticancer strategy. However, evidence for the occurrence of the Warburg effect in physiological processes has also been documented. As such, close consideration of which signaling pathways are beneficial targets and the effect of their inhibition on physiological processes are essential. The MAPK/ERK and MAPK/JNK pathways, crucial for normal cellular responses to extracellular stimuli, have recently emerged as key regulators of the Warburg effect during tumorigenesis and normal cellular functions. In this review, we summarize our current understanding of the roles of the ERK and JNK pathways in controlling the Warburg effect in cancer and discuss their implication in controlling this metabolic reprogramming in physiological processes and opportunities for targeting their downstream effectors for therapeutic purposes.
大多数肿瘤细胞由于癌基因和肿瘤抑制基因的突变而重新编程其葡萄糖代谢，导致参与细胞生长的信号通路的组成性激活。这种代谢重编程，称为有氧糖酵解或瓦伯格效应，使肿瘤细胞能够维持其快速增殖并逃避细胞凋亡。因此，干扰调节癌细胞中瓦伯格效应的致癌信号通路已成为一种有吸引力的抗癌策略。然而，也有证据表明瓦伯格效应发生在生理过程中。因此，必须仔细考虑哪些信号通路是有益的靶点，以及它们对生理过程的抑制作用。MAPK/ERK 和 MAPK/JNK 通路对于细胞对外界刺激的正常反应至关重要，它们最近已成为肿瘤发生和正常细胞功能过程中瓦伯格效应的关键调节因子。在这篇综述中，我们总结了我们目前对 ERK 和 JNK 通路在控制癌症中瓦伯格效应的作用的理解，并讨论了它们在控制生理过程中这种代谢重编程以及靶向它们的下游效应物用于治疗目的的机会中的意义。
