在癌症中,GOLPH3调节mTOR信号传递和拉巴胺素敏感性
Kenneth L Scott1, Omar Kabbarah, Mei-Chih Liang
1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Nature
|June 26, 2009
概括
一个频繁的5p13放大针对戈尔吉蛋白GOLPH3,被确定为一个强大的瘤基因. GOLPH3调节细胞大小和mTOR信号传递,影响癌症生长和对拉巴胺治疗的反应.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 在肺,卵巢,乳腺,前列腺和黑色素瘤等各种固体瘤中观察到频繁的5p13放大.
- 在放大5p13区域内,GOLPH3 (戈尔吉蛋白3) 作为候选基因出现.
研究的目的:
- 为了确定5p13放大所针对的特定基因.
- 为了功能性地描述GOLPH3作为潜在的瘤基因.
- 阐明GOLPH3有助于癌症发展和药物反应的机制.
主要方法:
- 5p13区域的综合基因组分析.
- 在体外和体外的功能增益和丧失研究.
- 生物化学分析以确定GOLPH3局部化和相互作用.
- 分析mTOR信号通路和对mTOR抑制剂的反应.
主要成果:
- 确定GOLPH3是5p13放大向的基因.
- GOLPH3作为一种强大的瘤基因,调节细胞大小并增强生长因子诱导的mTOR信号传递.
- GOLPH3 与逆转激素复合体相互作用,并影响对像拉巴胺素这样的mTOR抑制剂的反应.
结论:
- GOLPH3是一种新发现的瘤基因,在人类癌症中经常被放大.
- 通过调节mTOR通路,GOLPH3在癌细胞的增殖和生存中起着至关重要的作用.
- GOLPH3放大及其在mTOR信号传递中的作用表明了针对拉巴胺素反应的潜在治疗策略.
相关概念视频
mTOR 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...
mTOR 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...
PI3K/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...
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Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
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Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
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Small GTPases - Ras and Rho
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:
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The 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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