DRAP1/DR1抑制器复合体增加mTOR活动以促进进展,并在三阴性乳腺癌中赋予Everolimus敏感性
Min-Ying Huang1,2,3, Shu-Yuan Hu1,2,3, Jia Dong2
1Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
Cancer research
|May 15, 2024
概括
转录1-关联蛋白1 (DRAP1) 的降调器驱动了侵袭性三阴性乳腺癌 (TNBC) 的进展. 针对DRAP1/DR1复合体可能为TNBC患者提供新的治疗策略.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症遗传学 癌症遗传学
背景情况:
- 三阴性乳腺癌 (TNBC) 是一种具有攻击性的亚型,其特征是转录失调.
- 转录调节器在癌症进展中起着至关重要的作用,需要确定TNBC中的关键参与者.
研究的目的:
- 调查转录1关联蛋白1 (DRAP1) 的转录核心压缩器下调调剂在TNBC中的作用.
- 阐明DRAP1影响TNBC进展和治疗反应的分子机制.
主要方法:
- 在TNBC患者样本中对DRAP1表达的定量分析.
- 在体外测试评估DRAP1对TNBC细胞增殖,迁移和入侵的影响.
- 在体内研究评估DRAP1对瘤生长和转移的影响.
- 涉及DR1/DRAP1复合体,CASTOR1,mTOR信号传输和USP7介导的二维基化的机制研究.
主要成果:
- 在TNBC中DRAP1被上调,并与无复发性生存率差相关.
- DRAP1促进了TNBC的扩散,迁移,入侵,瘤生长和转移.
- DR1/DRAP1复合体抑制了CASTOR1的表达,从而激活了mTOR信号传递.
- DRAP1通过USP7增强DR1的稳定性,DR1促进DRAP1的转录,形成一个积极的反循环.
- DRAP1/DR1通路的激活使TNBC对Everolimus治疗产生敏感性.
结论:
- 一个DRAP1-DR1双向调节途径促进了TNBC的进展.
- 准DRAP1/DR1复合体是TNBC的一个潜在的治疗策略.
- 了解这种途径可以提高对TNBC病原体和mTOR抑制剂敏感性的洞察力.
相关概念视频
03:03mTOR 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
01:22PI3K/mTOR/AKT Signaling Pathway
3.5K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.5K
02:23Abnormal 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
01:15Receptor 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
01:23Negative Regulator Molecules
35.3K
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.
35.3K
01:24Regulation 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