通过PKCζ控制营养应激诱导的代谢重编程在瘤发生过程中
Li Ma1, Yongzhen Tao, Angeles Duran
1Sanford-Burnham Medical Research Institute, 10901 N. Torrey Pines Road, La Jolla, CA 92037, USA.
Cell
|February 5, 2013
概括
蛋白质激酶C zeta (PKCζ) 缺陷使癌细胞能够适应新陈代谢,通过血清蛋白生物合成途径利用谷氨. 损失PKCζ增强瘤生长,表明其作为代谢瘤抑制剂的作用.
科学领域:
- 在瘤学瘤学.
- 癌症新陈代谢 癌症新陈代谢
- 分子生物学分子生物学
背景情况:
- 瘤细胞表现出高代谢需求,并适应营养压力,以生存和增殖.
- 代谢重编程是癌症的标志性特征,在具有挑战性的条件下使持续增长成为可能.
研究的目的:
- 研究蛋白激酶C zeta (PKCζ) 在调节癌细胞代谢中的作用及其对瘤发生的影响.
- 阐明PKCζ影响癌细胞生存至关重要的代谢途径的分子机制.
主要方法:
- 研究了PKCζ缺乏对癌细胞代谢的影响,重点关注谷氨酸利用和血清蛋白生物合成途径.
- 分析了关键酶PHGDH和PSAT1的表达和活性,以应对PKCζ水平.
- 利用肠道瘤发生的小鼠模型和分析人类肠道瘤样本.
主要成果:
- 缺乏PKCζ促进了代谢可塑性,使得癌细胞能够在葡萄糖有限时通过血清蛋白生物合成途径使用谷氨.
- PKCζ抑制PHGDH和PSAT1的表达,并通过酸化抑制PHGDH的活性.
- 在小鼠中,PKCζ的丧失导致肠道瘤发生的增加以及PHGDH和PSAT1水平的升高.
- 人类癌症患者的低PKCζ水平与预后不佳相关,并与PHGDH水平相关.
结论:
- 在小鼠和人类癌症中,PKCζ作为一种关键的代谢性瘤抑制剂.
- 通过控制血清素生物合成途径,PKCζ调节癌细胞代谢,影响瘤生长和患者的治疗结果.
相关概念视频
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...
01:22PI3K/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
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
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
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...
02:23Abnormal Proliferation
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 daughter...
02:34Inhibition of Cdk Activity
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...