线粒体STAT3支持Ras-依赖的瘤转化
Daniel J Gough1, Alicia Corlett, Karni Schlessinger
1Department of Pathology and New York University Cancer Institute, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA.
概括
信号转换器和转录3激活器 (STAT3) 支持Ras驱动的癌症. 在STAT3中,我们可以使用STAT3.
科学领域:
- 分子生物学分子生物学
- 癌症研究 癌症研究
- 细胞生物学 细胞生物学
背景情况:
- 信号传感器和转录3激活器 (STAT3) 是一种通过酸化激活的转录因子.
- 通常,STAT3会转移到细胞核,以调节基因表达.
- 拉斯瘤蛋白是已知的恶性转变的驱动因素.
研究的目的:
- 研究STAT3在Ras介导恶性转变中的作用.
- 为了确定STAT3的正规核功能是否需要进行Ras转换.
- 探索STAT3在癌症中的非正规功能.
主要方法:
- 使用了Ras转化细胞模型.
- 使用的STAT3突变体具有酸化,核转位或DNA结合受损.
- 使用细胞生物学技术研究了STAT3局部化.
- 评估了代谢变化,包括糖解和氧化酸化.
主要成果:
- 在没有STAT3.3的情况下,Ras介导的转化受损.
- 缺乏正规功能的STAT3突变仍然支持Ras转换.
- 在线粒体中发现了STAT3,独立于核转位.
- 专门针对线粒体的STAT3促进了Ras转化.
- 线粒体STAT3调节了与癌症相关的代谢途径.
结论:
- 在Ras介导的恶性转变中,STAT3在核转录活动之外发挥着至关重要的作用.
- 在线粒体内,STAT3具有非正规的功能,支持癌症代谢.
- 线粒体STAT3直接参与了对癌细胞存活和增殖至关重要的代谢重编程.
相关概念视频
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.
Ras is a superfamily...
Ras is a superfamily...
MAPK Signaling Cascades
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
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...
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.
Ras is a superfamily...
Ras is a superfamily...


