通过STAT3/VEGF信号传递,REC8调节神经母细胞细胞的增殖,迁移,入侵和血管生成
Qiang Wang1, Wei Fan2, ZengHui Hao2
1Department of Pediatric Surgery, The Sixth Affiliated Hospital of Harbin Medical University, Harbin, 150001, China. doctor_wang@vip.163.com.
Journal of the Egyptian National Cancer Institute
|December 17, 2023
概括
准REC8,一个介质凝聚复合体中的蛋白质,显著抑制神经母细胞瘤的生长,迁移和血管生成. 击败REC8诱导细胞循环停止和细胞亡,为高风险神经母细胞瘤提供了一个有希望的治疗策略.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 神经母细胞瘤是一种普遍存在的儿童癌症,高风险病例的预后不佳.
- 介质凝聚复合体的组成部分REC8与各种恶性瘤有关.
- 确定新的治疗点对于改善神经母细胞瘤治疗结果至关重要.
研究的目的:
- 调查REC8淘汰对神经母细胞瘤细胞系 (SH-SY5Y和SK-N-AS) 的影响.
- 阐明REC8在神经母细胞瘤中的作用背后的分子机制.
- 评估REC8作为神经母细胞瘤的潜在治疗点.
主要方法:
- 小干扰 (si) RNA技术被用来击败REC8.8.
- 定量逆转录酶聚合酶连锁反应 (qRT-PCR) 和西部涂抹验证了REC8下调.
- 细胞计数工具-8 (CCK-8),流细胞计量,管形成试验和Transwell测试评估了细胞增殖,细胞循环,细胞亡,血管生成,迁移和入侵.
主要成果:
- 通过诱导G1阶段细胞循环停止,REC8下调显著减少神经母细胞细胞的增殖.
- Knockdown 的 REC8 抑制了细胞迁移,入侵和血管生成.
- 抑制REC8表达减少了神经母细胞瘤细胞中STAT3/VEGF信号通路的激活.
- 在神经母细胞瘤细胞中,REC8敲除增强了亡.
结论:
- 准REC8是神经母细胞瘤的潜在治疗策略.
- 对REC8的下调抑制了神经母细胞瘤中关键的致癌过程.
- 在STAT3/VEGF途径中REC8的作用表明了下游的治疗目标.
相关概念视频
Regulation of Angiogenesis and Blood Supply
2.6K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.6K
Receptor Downregulation in MVBs
2.1K
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
2.1K
Notch Signaling Pathway
4.3K
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
4.3K
mTOR Signaling and Cancer Progression
3.8K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.8K
Negative Regulator Molecules
35.4K
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
35.4K
Abnormal Proliferation
4.5K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.5K


