HSP90AA1通过促进CADM1表达和通过与FBXO7相互作用抑制PI3K-AKT通路来抑制清细胞细胞癌的进展
Wuping Yang1, Yifan Li2, Zhi Li3
1Department of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. yangwuping@zju.edu.cn.
Cell death discovery
|January 8, 2026
概括
热冲击蛋白90α家族A类成员1 (HSP90AA1) 在清细胞细胞癌 (ccRCC) 中被下调. 过度表达HSP90AA1通过调节FBXO7/CADM1/PI3K-AKT通路来抑制ccRCC的扩散和转移.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 热冲击蛋白90α家族A类成员1 (HSP90AA1) 与各种癌症有关,但其在清细胞细胞癌 (ccRCC) 中的作用尚不清楚.
- 了解HSP90AA1在ccRCC中的功能对于开发向疗法至关重要.
研究的目的:
- 研究ccRCC中HSP90AA1的表达模式,临床意义和生物功能.
- 阐明CCRCC进展中HSP90AA1的下游调节机制.
主要方法:
- 对HSP90AA1表达和临床意义的GEO和TCGA-KIRC数据库的分析.
- 免疫组织化学和西部涂抹验证ccRCC组织和细胞系中的HSP90AA1表达.
- 在体外 (殖民地形成,EDU,TUNEL,迁移,入侵试验) 和体内 (老鼠正位异种移植模型) 实验中,评估HSP90AA1的生物效应.
- 共同免疫沉 (Co-IP) 和RNA测序 (RNA-seq) 探索下游机制.
主要成果:
- 在ccRCC中,HSP90AA1显著下调,减少表达与瘤转移相关.
- 过度表达HSP90AA1抑制了ccRCC细胞的增殖和转移.
- HSP90AA1与F-box只有蛋白7 (FBXO7) 相互作用,增加了其表达. FBXO7下调与预后不佳有关.
- FBXO7促进了细胞粘附分子1 (CADM1) 的表达,并抑制了PI3K-AKT通路. HSP90AA1过度表达的影响被FBXO7敲击部分逆转,这降低了CADM1的调节,并激活了PI3K-AKT.
结论:
- 在ccRCC中,HSP90AA1充当瘤抑制剂,表现出低表达并抑制扩散和转移.
- HSP90AA1/FBXO7轴通过调节CADM1表达和PI3K-AKT信号通路来调节ccRCC进展.
相关概念视频
PI3K/mTOR/AKT Signaling Pathway
5.3K
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...
5.3K
mTOR Signaling and Cancer Progression
4.6K
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...
4.6K
Inhibition of Cdk Activity
5.5K
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
5.5K
Abnormal Proliferation
5.1K
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...
5.1K
The JAK-STAT Signaling Pathway
11.9K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
11.9K
Negative Regulator Molecules
38.2K
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.
38.2K


