在对营养压力的反应中,整合素αvβ3的上调促进了肺癌细胞的代谢可塑性
Arin Nam1, Shashi Jain1,2, Chengsheng Wu1
1Department of Pathology, Moores Cancer Center, and Sanford Consortium for Regenerative Medicine at the University of California, San Diego, La Jolla, California.
Cancer research
|April 8, 2024
概括
营养压力通过调节整合素αvβ3来重编程肺癌干细胞,从而激活持续的AMPK/PGC1α信号传递. 这种代谢适应促进了瘤的存活和发育,但向这种途径可以阻止癌症的进展.
科学领域:
- 癌症生物学 癌症生物学
- 代谢重编程 代谢重编程
- 瘤微环境 瘤微环境
背景情况:
- 癌症干细胞表现出显著的耐压力和代谢灵活性.
- 了解这些适应对于开发向癌症疗法至关重要.
研究的目的:
- 阐明营养压力促进癌症干细胞存活和非小细胞肺癌的代谢适应的分子机制.
- 确定潜在的治疗点,以抑制肺癌中的代谢重编程.
主要方法:
- 对培养细胞和人类非小细胞肺癌活检的分析.
- 研究了整合素αvβ3,AMP激活蛋白激酶 (AMPK) 和氧酶增殖器激活受体-玛协同激活器1α (PGC1α) 信号传递的作用.
- 在临床前小鼠模型中利用药理和遗传向策略.
主要成果:
- 营养应激会诱导整合素αvβ3的表达,从而导致持续的AMPK激活.
- 持续的AMPK激活促进了PGC1α的核定位,提高了谷氨酸代谢,TCA循环和氧化酸化的调节.
- 针对整合素αvβ3/AMPK/PGC1α轴有效地阻断了小鼠的瘤开始.
结论:
- 营养压力驱动了一种新的途径,涉及整合素αvβ3和持续的AMPK/PGC1α信号,用于肺癌干细胞的代谢重编程.
- 这一途径增强了新陈代谢的灵活性,支持瘤细胞的存活和启动.
- 这一轴的抑制是阻止肺癌进展的有希望的治疗策略.
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