细胞外的pyruvate kinase M2通过p-Tyr42 RhoA介导的超氧化物生成和上皮-介质细胞过渡诱导细胞迁移
Amir Hamza1, Jung Yoon Cho2, Kim Cuong Cap3
1Department of Biochemistry, Hallym University College of Medicine, Chuncheon, Kangwon-do, 24252, Republic of Korea.
Free radical biology & medicine
|September 18, 2023
概括
由巨细胞分泌的细胞外酸激酶M2 (PKM2) 通过增强癌细胞迁移和入侵来促进瘤的进展. 这通过RhoA/p47phox信号通路发生,增加超氧化物生产并激活上皮层-介质酶过渡 (EMT).
科学领域:
- 在瘤学瘤学.
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 癌细胞与瘤相关巨细胞 (TAMs) 之间的瘤微环境 (TME) 通信推动了癌症的进展.
- 由TAMs分泌的细胞外蛋白是这种相互作用的关键媒介.
研究的目的:
- 研究巨细胞分泌的细胞外蛋白在促进癌症进展中的作用.
- 在TME中识别参与癌细胞迁移,入侵和超氧化物生产的特定蛋白质.
主要方法:
- 癌细胞 (4T1) 和巨细胞 (Raw264.7) 的共同培养.
- 质谱学 (MALDI-TOF) 用于蛋白质的鉴定.
- 细胞迁移,入侵和超氧化物生产的功能测试.
- 西方涂抹和siRNA介导的基因沉默来分析信号通路.
- 基于抗体的抑制试验.
主要成果:
- 酸盐激酶M2 (PKM2) 被确定为巨细胞高度分泌的蛋白质.
- 细胞外PKM2增强了癌细胞的迁移,入侵和超氧化物生产.
- PKM2 与整合素α5/β1受体结合.
- PKM2诱导的超氧化物生成由RhoA和p47phox介导,涉及p47phox和RhoA的酸化.
- 细胞外PKM2调节表皮层-介质细胞过渡 (EMT) 标志物,通过化RhoA与ZEB1促进体结合的核转移.
结论:
- 由TAMs分泌的细胞外PKM2促进瘤发生.
- PKM2通过RhoA/p47phox信号通路促进癌细胞迁移和入侵.
- 在癌症治疗中,PKM2是潜在的治疗点.
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