罗亚激活促进葡萄糖吸收,以提高MAPK抑制剂耐药黑色素瘤细胞的增殖率
Vasanth Siruvallur Murali1,2, Divya Rajendran1,2, Tadamoto Isogai1,2
1Lyda Hill Department of Bioinformatics, UT Southwestern Medical Center, Dallas, TX, USA.
bioRxiv : the preprint server for biology
|January 23, 2024
概括
对像MAPKi这样的黑色素瘤治疗方法的耐药性可以通过准RhoA信号来克服. 抑制Rho-酶 (ROCK) 减少葡萄糖吸收和糖解,为长期癌症治疗提供了一种新的策略.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症新陈代谢 癌症新陈代谢
背景情况:
- 具有B-RafV600E突变的皮肤黑色素瘤被用MAPK抑制剂 (MAPKi) 治疗,但耐药性迅速发展.
- MAPKi耐药性与阿米类表型,增加的RhoA信号传递和增强的细胞收缩性有关.
- 罗基纳酶 (ROCK) 抑制剂可以逆转MAPKi耐药性,但潜在的机制尚不清楚.
结论:
- 一个新的机制揭示了高RhoA激活ROCK,导致IRS1/PI3K通路激活和GLUT1表达.
- 这一途径促进葡萄糖吸收和糖解,有助于黑色素瘤中MAPKi抵抗.
- ROCK 抑制剂是克服 MAPKi 耐药性的有希望的治疗策略,并改善长期黑色素瘤治疗结果.
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