Paul Sumana, Ghosh Saikat, Kumar Sushil
Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, 400076 Mumbai, India.
Neurosciences and Cellular and Structural Biology Division, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
Semin Cancer Biol. 2022 Nov;86(Pt 3):1216-1230. doi: 10.1016/j.semcancer.2022.09.007. Epub 2022 Oct 28.
Cancer cells undergo metabolic alterations to meet the immense demand for energy, building blocks, and redox potential. Tumors show glucose-avid and lactate-secreting behavior even in the presence of oxygen, a process known as aerobic glycolysis. Glycolysis is the backbone of cancer cell metabolism, and cancer cells have evolved various mechanisms to enhance it. Glucose metabolism is intertwined with other metabolic pathways, making cancer metabolism diverse and heterogeneous, where glycolysis plays a central role. Oncogenic signaling accelerates the metabolic activities of glycolytic enzymes, mainly by enhancing their expression or by post-translational modifications. Aerobic glycolysis ferments glucose into lactate which supports tumor growth and metastasis by various mechanisms. Herein, we focused on tumor glycolysis, especially its interactions with the pentose phosphate pathway, glutamine metabolism, one-carbon metabolism, and mitochondrial oxidation. Further, we describe the role and regulation of key glycolytic enzymes in cancer. We summarize the role of lactate, an end product of glycolysis, in tumor growth, and the metabolic adaptations during metastasis. Lastly, we briefly discuss limitations and future directions to improve our understanding of glucose metabolism in cancer.
癌细胞会发生代谢改变，以满足对能量、构建模块和氧化还原电位的巨大需求。肿瘤即使在有氧的情况下也表现出对葡萄糖的摄取和乳酸分泌行为，这一过程称为有氧糖酵解。糖酵解是癌细胞代谢的核心，癌细胞已经进化出各种机制来增强它。葡萄糖代谢与其他代谢途径相互交织，使得癌症代谢多样且异质，其中糖酵解起着核心作用。致癌信号主要通过增强糖酵解酶的表达或通过翻译后修饰来加速其代谢活性。有氧糖酵解将葡萄糖发酵成乳酸，乳酸通过各种机制支持肿瘤生长和转移。在此，我们重点关注肿瘤糖酵解，尤其是其与磷酸戊糖途径、谷氨酰胺代谢、一碳代谢和线粒体氧化的相互作用。此外，我们描述了关键糖酵解酶在癌症中的作用和调节。我们总结了糖酵解终产物乳酸在肿瘤生长中的作用以及转移过程中的代谢适应。最后，我们简要讨论了限制因素和未来方向，以增进我们对癌症中葡萄糖代谢的理解。
