Che Pulin, Yu Lei, Friedman Gregory K, Wang Meimei, Ke Xiaoxue, Wang Huafeng, Zhang Wenbin, Nabors Burt, Ding Qiang, Han Xiaosi
Department of Anesthesiology & Perioperative Medicine, Division of Molecular and Translational Biomedicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Guiyang Maternal and Child Health Hospital, Guiyang 550001, China.
Cancers (Basel). 2021 Mar 5;13(5):1111. doi: 10.3390/cancers13051111.
Metabolic reprogramming promotes glioblastoma cell migration and invasion. Integrin αvβ3 is one of the major integrin family members in glioblastoma multiforme cell surface mediating interactions with extracellular matrix proteins that are important for glioblastoma progression. The role of αvβ3 integrin in regulating metabolic reprogramming and its mechanism of action have not been determined in glioblastoma cells. Integrin αvβ3 engagement with osteopontin promotes glucose uptake and aerobic glycolysis, while inhibiting mitochondrial oxidative phosphorylation. Blocking or downregulation of integrin αvβ3 inhibits glucose uptake and aerobic glycolysis and promotes mitochondrial oxidative phosphorylation, resulting in decreased migration and growth in glioblastoma cells. Pharmacological inhibition of focal adhesion kinase (FAK) or downregulation of protein arginine methyltransferase 5 (PRMT5) blocks metabolic shift toward glycolysis and inhibits glioblastoma cell migration and invasion. These results support that integrin αvβ3 and osteopontin engagement plays an important role in promoting the metabolic shift toward glycolysis and inhibiting mitochondria oxidative phosphorylation in glioblastoma cells. The metabolic shift in cell energy metabolism is coupled to changes in migration, invasion, and growth, which are mediated by downstream FAK and PRMT5 in glioblastoma cells.
代谢重编程促进胶质母细胞瘤细胞的迁移和侵袭。整合素αvβ3是多形性胶质母细胞瘤细胞表面主要的整合素家族成员之一，介导与细胞外基质蛋白的相互作用，而这些相互作用对胶质母细胞瘤的进展很重要。在胶质母细胞瘤细胞中，αvβ3整合素在调节代谢重编程中的作用及其作用机制尚未明确。整合素αvβ3与骨桥蛋白结合可促进葡萄糖摄取和有氧糖酵解，同时抑制线粒体氧化磷酸化。阻断或下调整合素αvβ3可抑制葡萄糖摄取和有氧糖酵解，并促进线粒体氧化磷酸化，导致胶质母细胞瘤细胞的迁移和生长减少。对黏着斑激酶（FAK）的药理学抑制或蛋白精氨酸甲基转移酶5（PRMT5）的下调可阻断向糖酵解的代谢转变，并抑制胶质母细胞瘤细胞的迁移和侵袭。这些结果支持整合素αvβ3与骨桥蛋白的结合在促进胶质母细胞瘤细胞向糖酵解的代谢转变和抑制线粒体氧化磷酸化中起重要作用。细胞能量代谢的这种代谢转变与迁移、侵袭和生长的变化相关联，而这些变化在胶质母细胞瘤细胞中由下游的FAK和PRMT5介导。
