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结肠直肠多增加了糖溶性活性.
Egle Rebane-Klemm1,2, Leenu Reinsalu1,2, Marju Puurand1
1Laboratory of Chemical Biology, National Institute of Chemical Physics and Biophysics, Tallinn, Estonia.
Frontiers in oncology
|June 21, 2023
概括
结肠直肠多体显示增加的葡萄糖分解和功能呼吸,与瘤不同. 聚发育期间的代谢转变可能提供早期癌症检测和治疗点.
科学领域:
- 生物化学 生物化学
- 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:
- 结肠直肠癌 (CRC) 的能量代谢尚未完全理解,研究表明它依赖于线粒体呼吸而不是纯糖解.
- 在从正常组织过渡到多体,然后到CRC的过程中发生的代谢变化在很大程度上是未被探索的.
- 在瘤发生过程中识别代谢适应可能会导致早期诊断生物标志物和新的治疗策略.
研究的目的:
- 研究和描述发生在结肠直肠癌 (CRC) 发育过程中的代谢重编程,从癌前多到瘤.
- 为了比较多体,CRC组织和正常组织的生物能量表型.
- 为了确定与CRC发育中的代谢适应相关的分子和功能变化.
主要方法:
- 使用高分辨率呼吸计来评估细胞呼吸和线粒体功能.
- 使用定量逆转录PCR (qRT-PCR) 来测量基因表达水平.
- 分析了人类结直肠癌和多组织样本.
主要成果:
- 与CRC瘤和正常组织相比,结肠多体表现出更高的甘油性生物能量表型.
- 在多重体中观察到关键的甘油性基因 (GLUT1,HK,LDHA,MCT) 的表达增加.
- 尽管增强了糖解,但多细胞保持了高度功能性的氧化酸化 (OXPHOS) 系统.
- 细胞内能量转移通路被重新排列成多,增加了腺酸酶 (AK) 和肌酸酶 (CK) 异型的表达.
- CRC的发展与降低葡萄糖分解,维持OXPHOS以及CK和特定AK异型 (AK1,AK2) 的降低调节有关.
结论:
- 结直肠多体呈现出明显的代谢特征,其特征是增加糖解与功能性OXPHOS相结合.
- 聚形成期间的代谢重编程涉及细胞内能量传递系统的改变.
- 转向降低糖解和改变能量传输途径的转变似乎对CRC进展至关重要.
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