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関連する概念動画

Notch Signaling Pathway03:14

Notch Signaling Pathway

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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...
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Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

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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...
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Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

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Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
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Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

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Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
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The Retinoblastoma Gene01:20

The Retinoblastoma Gene

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Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
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Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

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Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
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このページは機械翻訳されています。他のページは英語で表示される場合があります。View in English
  1. ホーム
  2. 研究分野
  3. 生物医学と臨床科学
  4. 腫瘍学とがん発生
  5. 分子標的
  6. Notch2の損失は,小細胞肺がんにおいてtrim28依存の脆弱性を生み出します.
  1. ホーム
  2. 研究分野
  3. 生物医学と臨床科学
  4. 腫瘍学とがん発生
  5. 分子標的
  6. Notch2の損失は,小細胞肺がんにおいてtrim28依存の脆弱性を生み出します.

関連する実験動画

Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer
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Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer

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NOTCH2の損失は,小細胞肺がんにおいてTRIM28依存の脆弱性を生み出します.

Deli Hong1, Ying Lyu2, Richa Nayak2

  • 1Department of Medical Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA.

Developmental cell
|August 27, 2025

PubMed で要約を見る

まとめ
この要約は機械生成です。

小細胞肺がん (SCLC) の研究者は,NOTCH2が失われると,TRIM28が腫瘍の成長に不可欠であることを発見しました. TRIM28をターゲットにすることで,NOTCH2欠乏性SCLCに対する新しい治療法を提供することができる.

キーワード:
CRISPR-Cas9スクリーニングNOTCH2 についてトリム28内生レトロウイルス

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Author Spotlight: Finding New Therapeutic Targets for Malignant Peripheral Nerve Sheath Tumor Through Genome-Scale shRNA Screens
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Cell Aggregation Assays to Evaluate the Binding of the Drosophila Notch with Trans-Ligands and its Inhibition by Cis-Ligands
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Cell Aggregation Assays to Evaluate the Binding of the Drosophila Notch with Trans-Ligands and its Inhibition by Cis-Ligands

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関連する実験動画

Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer
09:08

Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer

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Author Spotlight: Finding New Therapeutic Targets for Malignant Peripheral Nerve Sheath Tumor Through Genome-Scale shRNA Screens
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Cell Aggregation Assays to Evaluate the Binding of the Drosophila Notch with Trans-Ligands and its Inhibition by Cis-Ligands
05:48

Cell Aggregation Assays to Evaluate the Binding of the Drosophila Notch with Trans-Ligands and its Inhibition by Cis-Ligands

Published on: January 2, 2018

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科学分野:

  • 腫瘍学
  • 分子生物学
  • 遺伝学

背景:

  • 小細胞肺がん (SCLC) は攻撃的な悪性腫瘍で,標的治療は限られている.
  • NOTCH1/NOTCH2変異は,SCLCの約15%で発生し,しばしば低NOTCH活性と相関する.

研究 の 目的:

  • SCLCにおいて,特にNOTCH経路の変化を有する腫瘍において,新しい治療標的を特定する.
  • SCLCにおけるNOTCH2不活性化の機能的影響を調査する.

主な方法:

  • CRISPR-Cas9スクリーニングは,SCLCの遺伝子組み換えマウスモデルからのプライマリ細胞ラインで行われます.
  • 遺伝子発現,ウイルス感知経路,インターフェロン反応の分析
  • STING-MAVS-TBK1信号軸の調査

主要な成果:

  • TRIM28は,NOTCH2不活性化SCLCにおける合成的致死性依存症として特定された.
  • TRIM28の喪失は内生レトロウイルス (ERV) を誘発し,ウイルスセンサーを活性化し,タイプIインターフェロン反応を誘発した.
  • TRIM28の喪失は,STING-MAVS-TBK1軸経由でハイパー依存を生み出し,NOTCH2が失われた場合にのみ腫瘍の成長に不可欠でした.
小細胞肺がん
合成による死亡率
ウイルス検出

結論:

  • TRIM28はNOTCH2欠乏性SCLCにおける重大な脆弱性である.
  • TRIM28は,NOTCH2変異を有するSCLC患者のサブセットにおける潜在的な治療目標です.