MIF/NR3C2轴通过MAPK-ERK和AP-1通路调节胰腺癌中的葡萄糖代谢重编程
Shouhui Yang1, Wei Tang2, Azadeh Azizian3
1Pancreatic Cancer Section, Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Carcinogenesis
|April 17, 2024
概括
巨细胞迁移抑制因子 (MIF) 通过通过HK1,HK2和LDHA升调葡萄糖代谢来促进胰腺癌的生长. 核受体子家族3组C成员2 (NR3C2) 抵消了这种效应,提供了一个潜在的治疗点.
科学领域:
- 在瘤学瘤学.
- 癌症新陈代谢 癌症新陈代谢
- 分子生物学分子生物学
背景情况:
- 炎症和细胞代谢的改变是癌症的关键标志.
- 在胰腺管腺癌 (PDAC) 中,炎症信号和代谢变化相互联系,推动疾病的进展.
- 在胰腺癌的代谢重编程中炎症调解者的精确作用仍然不完全理解.
研究的目的:
- 调查巨细胞迁移抑制因子 (MIF) 和核受体亚家族3组C成员2 (NR3C2) 在调节胰腺癌中的代谢重编程中的相互作用作用.
- 阐明MIF和NR3C2在PDAC中影响葡萄糖代谢和瘤进展的机制.
主要方法:
- 在PDAC患者中分析MIF和NR3C2表达与糖分酶 (HK1,HK2,LDHA) 水平的相关性.
- 使用胰腺癌细胞系进行体外研究,以评估MIF和NR3C2对葡萄糖吸收和乳酸盐生产的影响.
- 在体内实验中,使用PDAC的小鼠模型来验证这些发现.
- 研究涉及的信号通路,包括MAPK-ERK和AP-1.
主要成果:
- MIF与基酶1 (HK1),基酶2 (HK2) 和乳酸脱酶A (LDHA) 的表达增加呈正相关性,导致PDAC中酸盐和乳酸盐水平升高.
- 在胰腺癌细胞和小鼠模型中,MIF通过上调HK1,HK2和LDHA来增强葡萄糖吸收和乳酸流量.
- 相反,高NR3C2表达与降低HK1,HK2和LDHA水平有关,抑制葡萄糖吸收和乳酸流量.
- 由MIF驱动的代谢变化包括激活基因激活蛋白激酶-ERK通路,而NR3C2与激活蛋白1相互作用.
结论:
- MIF/NR3C2轴在调节葡萄糖代谢方面发挥着关键的交互作用,支持PDAC瘤生长和进展.
- 向MIF/NR3C2通路为开发新型治疗方法以改善胰腺癌的结果提供了潜在的战略.
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