GOLPH3は,mTORシグナル伝達と癌におけるラパミシン感受性を調節する
Kenneth L Scott1, Omar Kabbarah, Mei-Chih Liang
1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Nature
|June 26, 2009
まとめ
頻度の高い5p13増幅は,強力な腫瘍遺伝子の1つとして識別されたGolgiタンパク質GOLPH3を標的とする. GOLPH3は細胞サイズとmTORシグナル伝達を調節し,がんの成長とラパミシン治療への反応に影響を与えます.
科学分野:
- 腫瘍学 腫瘍学
- 分子生物学は分子生物学である.
- 遺伝学 遺伝学とは
背景:
- 肺,卵巣,乳腺,前立腺,メラノーマなどの様々な固体腫瘍で観察された頻繁な5p13増幅.
- GOLPH3 (Golgi phosphoprotein 3) は,増幅された5p13領域内の候補遺伝子として現れる.
研究 の 目的:
- 5p13増幅によって標的となる特定の遺伝子を特定するために.
- 潜在的腫瘍遺伝子としてGOLPH3を機能的に特徴づける.
- GOLPH3ががんの発症と薬剤反応に寄与するメカニズムを解明する.
主な方法:
- 5p13地域の統合的ゲノムプロファイリング.
- 機能の獲得と喪失に関するインビトロおよびインビボの研究.
- GOLPH3の局所化と相互作用を決定するための生化学的分析.
- mTORシグナル伝達経路と,mTOR阻害剤に対する反応の分析.
主要な成果:
- GOLPH3は,5p13増幅によって標的となる遺伝子として特定されました.
- GOLPH3は強力な腫瘍遺伝子として機能し,細胞サイズを調節し,成長因子誘発 mTORシグナル伝達を強化します.
- GOLPH3はレトロマー複合体と相互作用し,ラパミシンなどのmTOR阻害剤に対する反応に影響を与えます.
結論:
- GOLPH3は,ヒトの癌で頻繁に増幅される,新たに特定された腫瘍遺伝子です.
- GOLPH3は,mTOR経路の調節を通じて,がん細胞の増殖と生存に重要な役割を果たしています.
- GOLPH3増幅とmTORシグナル伝達におけるその役割は,ラパミシン反応を標的とした潜在的な治療戦略を示唆する.
関連する概念動画
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...
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03:03mTOR Signaling and Cancer Progression
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The mTOR pathway or the...
The mTOR pathway or the...
01:22PI3K/mTOR/AKT Signaling Pathway
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 rapamycin-insensitive companion...
01:19Interactions Between Signaling Pathways
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01:24Small GTPases - Ras and Rho
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02:38The Ras Gene
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.
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