基因素甲基转移酶NSD3 通过与PPP1CB相互作用抑制肺腺癌糖解,从而降低STAT3信号通路
Yanling Zhou1,2, Xintong Peng3,4, Cheng Fang5
1Department of Oncology, Institute of Medical Sciences, National Clinical Research Center for Geriatric Disorders, Institue of Medical Sciences, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|August 9, 2024
概括
希斯甲基转移酶NSD3通过抑制糖分解来抑制肺腺癌的生长和扩散. 这项研究揭示了NSD3.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 基因组甲基转移酶NSD3 (含有3的核受体SET域) 在癌症中经常发生变化.
- 目前尚不完全了解NSD3在癌症发病和进展中的作用.
研究的目的:
- 为了研究NSD3在肺腺癌中的功能.
- 阐明NSD3影响癌症进展的机制.
主要方法:
- 在肺腺癌模型中的体内研究.
- 分析NSD3表达与临床特征和存活率的相关性.
- 研究NSD3对糖解,扩散,迁移和入侵的影响.
- 涉及NSD3,PPP1CB和p-STAT3.3的蛋白质与蛋白质相互作用研究.
- 对蛋白质酸化的环境因素 (CO2,pH) 的评估.
主要成果:
- 下调的NSD3水平与肺腺癌的不良预后相关.
- 在体内,NSD3抑制了瘤的扩散,迁移和入侵.
- 通过减少HK2转化和葡萄糖吸收,NSD3抑制糖解.
- NSD3与PPP1CB和p-STAT3形成一个复合体,使p-STAT3脱,抑制HK2转录.
- PPP1CB酸化受CO2和pH水平的影响.
结论:
- 在抑制肺腺癌中,NSD3起着关键的非表观遗传作用.
- 通过NSD3/PPP1CB/p-STAT3通路,NSD3调节了STAT3依赖的糖解.
- 针对NSD3/PPP1CB/p-STAT3轴为肺腺癌提供了一个潜在的治疗策略.
相关概念视频
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
01:20The JAK-STAT Signaling Pathway
8.7K
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...
8.7K
01:12Role Of Notch Signalling In Intestinal Stem Cell Renewal
2.1K
Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
2.1K
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
02:34Inhibition of Cdk Activity
4.7K
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...
4.7K
01:23Negative Regulator Molecules
35.2K
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.
35.2K