ミュータント・クラスのコピー番号は 代謝再プログラムと治療感受性を定義する
Emma M Kerr1, Edoardo Gaude1, Frances K Turrell1
1MRC Cancer Unit, University of Cambridge, Box 197, Cambridge Biomedical Campus, Cambridge CB2 0XZ, UK.
Nature
|February 25, 2016
まとめ
肺がんにおけるRAS/MAPK経路の緩和は,KRAS変異を含む. KRAS複製が増加した腫瘍は,異なる代謝プロファイルを示し,Kras変異性肺がんの異なる治療戦略を示唆する.
科学分野:
- 腫瘍学
- 分子生物学
- 癌 代謝
背景:
- RAS/MAPKシグナル伝達経路は,非小細胞肺がん (NSCLC) で頻繁に変化し,しばしばKRAS変異によって引き起こされます.
- 単一の突然変異のKrasアレルはマウスの肺腫瘍を誘発しますが,進行にはKras複製数の増加を含むさらなる遺伝的変化が必要です.
研究 の 目的:
- 肺がんにおける異なるKras遺伝子型 (ホモジゴス対ヘテロジゴス) の現象的および代謝的差異を調査する.
- カラスのアレル濃縮が腫瘍代謝と治療の脆弱性に影響するかどうかを決定する.
主な方法:
- ネズミの胚性線維芽細胞と肺がん細胞のKras(G12D/G12D) とKras(G12D/+) の比較分析
- グルコース代謝,トリカルボキシル酸サイクル活性,グルタチオンの生物合成を含む代謝プロファイリング.
- クラスのアレル含有量が変化するマウスの自発的な肺腫瘍を用いた in vivo 研究.
主要な成果:
- Kras ((G12D/G12D) 細胞は,解毒のための糖分解と強化されたグルタチオンの合成に向けて代謝のシフトを示します.
- この代謝再配線は,進行したクロス型同胞性NSCLCおよびクロス型複製増殖による自発的なマウンの肺腫瘍で観察されるが,初期段階の腫瘍では観察されない.
- ミュータント・クラスのコピー・ゲインは 積極的な肺腫瘍において 特定の代謝依存性を生み出します
結論:
- 変異したKRAS肺腫瘍は異質で,異なる代謝プロファイル,予後,およびアレル含有量に基づく治療感受性があります.
- 肺がんの進行中に重要な代謝変化を誘導する.
- これらの独特な代謝依存症をターゲットにすることで,攻撃的な突然変異性KRAS肺がんの治療のための潜在的な戦略が提供されます.
さらに関連する動画
07:49Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
Published on: July 17, 2019
6.6K
10:13A Multiplexed Luciferase-based Screening Platform for Interrogating Cancer-associated Signal Transduction in Cultured Cells
Published on: July 3, 2013
11.7K
関連する概念動画
The Ras Gene
7.5K
The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
Ras is a...
7.5K
Abnormal Proliferation
5.4K
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...
5.4K
Small GTPases - Ras and Rho
5.7K
Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
Three regulatory proteins control their activity:
5.7K
Treatment Resistant Cancers
3.9K
Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.9K
Cancer-Critical Genes I: Proto-oncogenes
11.8K
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...
11.8K
The Ras Gene
2.4K
2.4K
