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相关概念视频

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The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
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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.
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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...
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Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
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Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
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Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
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通过增强AXIN1介导的Smad7降解,TRAF2降低促进了MAFLD-HCC中的TGF-β-mTORC1信号.

Zhonglin Li1, Jinfang Zhao1, Ya Wu2

  • 1Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

FASEB journal : official publication of the Federation of American Societies for Experimental Biology
|February 16, 2024
PubMed
概括

瘤坏死因子受体相关因子2 (TRAF2) 缺乏通过增强TGF-β-mTORC1通路,促进代谢相关的脂肪肝疾病 (MAFLD) 和肝细胞癌 (HCC). 减少TRAF2加速了MAFLD-HCC中的瘤生长.

关键词:
在AXIN1中,AXIN1是AXIN1的前身.马夫尔德 (MAFLD) 是一个在TGF-β的基础上.在TRAF2中,肝炎肝炎是一种肝炎.在 mTORC1 的情况下,mTORC1 是 mTORC1.

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科学领域:

  • 肝病学和癌症生物学 肝病学和癌症生物学
  • 肝脏疾病的分子机制
  • 瘤发生的发生因子.

背景情况:

  • 代谢相关的脂肪肝疾病 (MAFLD) 是肝细胞癌 (HCC) 的一个不断增长的原因.
  • 连接MAFLD与HCC的精确分子通路仍然不完全理解.
  • 瘤坏死因子受体相关因子2 (TRAF2) 与癌症相关的炎症信号通路有关.

研究的目的:

  • 调查TRAF2在MAFLD相关HCC.病变发生过程中的作用和分子功能.
  • 阐明在MAFLD-HCC中受TRAF2失调影响的信号通路.

主要方法:

  • 使用了TRAF2淘汰赛 (TRAF2-/-) 和野生型 (TRAF2+/+) Huh7细胞和Tgfbr2ΔHep小鼠.
  • 用转化生长因子-β (TGF-β) 刺激细胞,并分析糖解和脂质合成.
  • 使用共免疫沉 (co-IP) 来研究蛋白质相互作用和降解途径.
  • 在高脂肪饮食 (HFD) 上给TRAF2-/-小鼠注射PLX-4720.

主要成果:

  • 在TGF-β刺激后,TRAF2-/-细胞表现出增强的瘤形成.
  • 证实TGF-β信号传递对MAFLD-HCC发展至关重要.
  • 在TGF-β的影响下,TRAF2缺乏导致糖解,脂质合成和拉巴胺素复合物1 (mTORC1) 激活的机械点增加.
  • 失去TRAF2促进了AXIN1介导的Smad7降解,从而增强了TGF-β信号传递.
  • 在TRAF2-/-小鼠中,PLX-4720治疗抑制了HFD的瘤增殖.

结论:

  • 在MAFLD-HCC中,TRAF2起着至关重要的保护作用.
  • 减少TRAF2表达会通过激活TGF-β-mTORC1通路通过增强的AXIN1-介导的Smad7降解来加剧MAFLD-HCC.
  • 用像PLX-4720这样的药物向AXIN1可能为MAFLD-HCC提供治疗策略.