機能的ゲノミクスは,セリン合成経路が乳がんにおいて不可欠であることを明らかにしています
Richard Possemato1, Kevin M Marks, Yoav D Shaul
1Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, Massachusetts 02142, USA.
Nature
|July 16, 2011
まとめ
研究者らは,フォスフォグリセラート脱水素酶 (PHGDH) を,攻撃的な乳がんにおける重要な代謝標的として特定した. PHGDHを抑制すると,血清素合成経路とグルタミン類の代謝を vivo で妨害することで,腫瘍の成長が止まります.
科学分野:
- 腫瘍学 腫瘍学
- メタボリック経路は
- 遺伝子機能 遺伝子機能
背景:
- 癌細胞は,成長と増殖のために代謝を再プログラムします.
- RNA干渉 (RNAi) スクリーニングは,がんの標的を特定するための強力なツールです.
- In vivoスクリーニングモデルは,腫瘍発生を理解するために不可欠です.
研究 の 目的:
- 新しいがん標的を特定するために,ネガティブ選択RNAiスクリーニング方法を開発し,適用する.
- 乳がんの生体内成長に不可欠な代謝遺伝子を特定する.
- 乳がんにおけるフォスフォグリセラート脱水素酵素 (PHGDH) の役割を調査する.
主な方法:
- ヒト乳がんの異種移植モデルを用いた,内生陰性選択RNAiスクリーニング方法を開発した.
- 攻撃的な乳がんと茎性に関連した代謝遺伝子をスクリーニングしました.
- 乳がん細胞系におけるPHGDH発現を抑制するためにRNA干渉を利用した.
主要な成果:
- 活体腫瘍発生における重要な遺伝子として,フォスフォグリセラート脱水素酶 (PHGDH) を特定した.
- PHGDHはER陰性乳がんにおいて過剰発現し,セリン生物合成を誘導する.
- PHGDH抑制は細胞増殖とセリン合成を低下させ,TCAサイクルアナプレロシスに影響を与えました.
- PHGDH抑制により,TCAサイクルの中間物質であるアルファケトグルタレート濃度が低下した.
結論:
- 特定の乳がんは,成長のためのPHGDH駆動のセリン合成経路の流れに依存しています.
- PHGDHは,攻撃的な乳がんの潜在的治療標的である.
- In vivo ネガティブセレクションRNAiスクリーンは,抗がん標的の発見に有効です.
さらに関連する動画
07:48Utilizing Functional Genomics Screening to Identify Potentially Novel Drug Targets in Cancer Cell Spheroid Cultures
Published on: December 26, 2016
11:13Exploring the Pharmacological Action and Molecular Mechanism of Salidroside in Inhibiting MCF-7 Cell Proliferation and Migration
Published on: June 9, 2023
関連する概念動画
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
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...
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...
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
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...
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...
03:03mTOR Signaling and Cancer Progression
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...
03:03mTOR Signaling and Cancer Progression
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...
01:33Cancer-Critical Genes I: Proto-oncogenes
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...
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...
01:33Cancer-Critical Genes I: Proto-oncogenes
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...
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...