一个可用药物的级联链接 metionin代谢与表观基因组重编程在状细胞癌
Chehyun Nam1, Li-Yan Li2,3, Qian Yang3
1Center for Craniofacial Molecular Biology, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90033.
概括
上部空气消化状细胞癌 (UASCC) 由于LAT1载体而显示高氨酸水平. 针对这种氨酸-EZH2轴为这种攻击性癌症提供了新的治疗策略.
科学领域:
- 在瘤学瘤学.
- 生物化学 生物化学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 上部气消化层状细胞癌 (UASCC) 是一种具有有限治疗选择的侵袭性癌症.
- 氨基酸代谢,特别是氨酸,在癌症进展中起着至关重要的作用.
研究的目的:
- 研究氨酸代谢及其载体LAT1在UASCC中的作用.
- 在已识别的代谢途径内确定治疗点.
主要方法:
- 在UASCC中分析氨酸水平和LAT1载体表达.
- 通过TP63/KLF5/SREBF1.1.研究了LAT1的转录调节.
- 生物信息选用于识别LAT1-氨酸路径的下游目标.
- 使用患者衍生瘤器官和体内模型进行验证.
主要成果:
- 在人类癌症中,UASCC表现出最高的氨酸水平,这是由高LAT1表达驱动的.
- 通过UASCC特定的调节器,LAT1被转录激活.
- EZH2被确定为一个关键的下游目标,将 metionin代谢与表观基因组重编程联系起来.
- LAT1-氨酸-EZH2级联对UASCC细胞生存和增殖至关重要.
- LAT1表达与针对这一轴的灵敏度相关.
结论:
- 通过LAT1-methionine-EZH2轴,氨酸代谢和表观基因组重编程之间的独特交叉对UASCC至关重要.
- 这一途径代表了瘤特定的脆弱性,可以通过药理或饮食干预来利用.
相关概念视频
Epigenetic Regulation
3.0K
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
X-chromosome...
3.0K
Phase II Reactions: Methylation Reactions
177
Methylation is a phase II biotransformation process involving the attachment of a methyl group to a substrate. Enzymes known as methyltransferases orchestrate this reaction.
The mechanism of methylation unfolds in two stages. The first stage sees a methyltransferase enzyme facilitating the transfer of a methyl group from S-adenosylmethionine (SAM) to the substrate, forming S-adenosylhomocysteine (SAH). The second stage involves further metabolism of SAH into homocysteine, which can be recycled...
The mechanism of methylation unfolds in two stages. The first stage sees a methyltransferase enzyme facilitating the transfer of a methyl group from S-adenosylmethionine (SAM) to the substrate, forming S-adenosylhomocysteine (SAH). The second stage involves further metabolism of SAH into homocysteine, which can be recycled...
177
Metastasis
5.5K
Metastasis is the spread of cancer cells from the original site to distant locations in the body. Cancer cells can spread via blood vessels (hematogenous) as well as lymph vessels in the body.
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
5.5K
Mitogens and the Cell Cycle
6.5K
Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
6.5K
Covalently Linked Protein Regulators
6.8K
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
These groups modify specific amino acids in a protein....
6.8K
Induced Pluripotent Stem Cells
4.0K
Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic...
Somatic...
4.0K


