Integrin αvβ3 Engagement Regulates Glucose Metabolism and Migration through Focal Adhesion Kinase (FAK) and Protein Arginine Methyltransferase 5 (PRMT5) in Glioblastoma Cells.
Integrin αvβ3 Engagement Regulates Glucose Metabolism and Migration through Focal Adhesion Kinase (FAK) and Protein Arginine Methyltransferase 5 (PRMT5) in Glioblastoma Cells.
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DOI：
10.3390/cancers13051111
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发表时间：
2021-03-05
期刊：
影响因子：
5.2
通讯作者：
Han X
中科院分区：
文献类型：
--
作者：
Che P;Yu L;Friedman GK;Wang M;Ke X;Wang H;Zhang W;Nabors B;Ding Q;Han X
整合素与细胞外基质的相互作用在癌细胞的迁移、侵袭和生长中起着关键作用。然而，整合素参与是否通过代谢重编程促进癌症进展尚不完全清楚。本研究探讨整合素αvβ3与其配体结合在代谢重编程中的作用和机制。这些数据支持整合素αvβ3在胶质母细胞瘤细胞葡萄糖摄取和有氧糖酵解增加以及线粒体氧化磷酸化减少中起重要作用。此外，这些数据表明粘着斑激酶和精氨酸甲基转移酶5可能是整合素αvβ3的下游效应因子，并调节代谢向糖酵解的转变。这些发现为癌症细胞如何根据整合素和细胞外基质蛋白传递的微环境信号调节其代谢提供了新的见解，以及这些信号最终如何转化为代谢修饰以及细胞行为的变化，包括迁移、侵袭和生长。代谢重编程促进胶质母细胞瘤细胞迁移和侵袭。整合素αvβ3是多形性胶质母细胞瘤细胞表面的主要整合素家族成员之一，它介导与细胞外基质蛋白的相互作用，在胶质母细胞瘤的发展中起重要作用。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确定。整合素αvβ3与骨桥蛋白结合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抑制葡萄糖摄取和有氧糖酵解，促进线粒体氧化磷酸化，导致胶质母细胞瘤细胞迁移和生长减少。药物抑制粘着斑激酶(FAK)或下调蛋白精氨酸甲基转移酶5(PRMT5)可阻断代谢向糖酵解的转变，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和骨桥蛋白的结合在促进胶质母细胞瘤细胞代谢向糖酵解转变和抑制线粒体氧化磷酸化方面发挥重要作用。细胞能量代谢的变化与迁移、侵袭和生长的变化有关，这些变化是由胶质母细胞瘤细胞中下游的FAK和PRMT5介导的。
Interactions of integrins with the extracellular matrix play a key role in cancer cell migration, invasion, and growth. However, whether integrin engagement promotes cancer progression through metabolic reprogramming has not been completely understood. This study investigates the role and mechanism of integrin αvβ3 engagement with its ligand in metabolic reprogramming. The data support that integrin αvβ3 plays an important role in increased glucose uptake and aerobic glycolysis, as well as in decreased mitochondrial oxidative phosphorylation, in glioblastoma cells. In addition, the data imply that focal adhesion kinase (FAK) and protein arginine methyltransferase 5 (PRMT5) are likely downstream effectors of integrin αvβ3, and regulate metabolic shift toward glycolysis. These findings provide new insight into how cancer cells regulate their metabolism based on microenvironmental cues transmitted by integrin and extracellular matrix proteins, and how the signals eventually translate to metabolic modifications coupled with changes in cell behavior, including migration, invasion, and growth. 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.
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影响因子：
5.7
作者：
Golubovskaya VM;Huang G;Ho B;Yemma M;Morrison CD;Lee J;Eliceiri BP;Cance WG
通讯作者：
Cance WG
影响因子：
--
作者：
Eckert, Dawid;Biermann, Katharina;Nettersheim, Daniel;Gillis, Ad J. M.;Steger, Klaus;Jaeck, Hans-Martin;Mueller, Annette M.;Looijenga, Leendert H. J.;Schorle, Hubert
通讯作者：
Schorle, Hubert
影响因子：
5.9
作者：
Keibler MA;Wasylenko TM;Kelleher JK;Iliopoulos O;Vander Heiden MG;Stephanopoulos G
通讯作者：
Stephanopoulos G
影响因子：
64.5
作者：
Brooks, PC;Stromblad, S;Cheresh, DA
通讯作者：
Cheresh, DA
影响因子：
8
作者：
Hecker, TP;Ding, Q;Gladson, CL
通讯作者：
Gladson, CL