Lysophosphatidylcholine 乙转移酶 1 抑制了纳米聚类和 KRAS 的功能
Neha Arora1, Hong Liang1, Wantong Yao2
1Department of Integrative Biology and Pharmacology, McGovern Medical School, University of Texas Health Science Center, Houston, Texas, USA.
bioRxiv : the preprint server for biology
|June 10, 2024
概括
酸酸胆转移酶1 (LPCAT1) 重塑酸胺素 (PS) 酸链抑制KRAS瘤信号和瘤生长. 这表明LPCAT1是KRAS突变癌症的治疗点.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 克拉斯突变导致20%的人类癌症,包括胰腺癌,结直肠癌和肺癌.
- 瘤性KRAS信号被细分为与特定的脂酸 (PS) 脂质丰富的血膜纳米集群.
- 向KRAS瘤发生可能涉及调节这些信号平台.
研究的目的:
- 调查酸胺 (PS) 乙烯链重塑在抑制KRAS瘤发生中的作用.
- 探索酸酸胆转移酶 (LPCATs) 的潜力,特别是LPCAT1,作为治疗调节剂.
主要方法:
- 在癌细胞系中稳定表达LPCAT1,以改变PS乙烯链的组成.
- 分析KRAS纳米集群,信号和瘤活性.
- 对KRAS抑制剂的敏感性评估和患者数据的统计分析.
主要成果:
- LPCAT1的表达削弱了不和的sn-2酸链PS物种,并破坏了KRASG12V纳米集群.
- 影响LPCAT1表达的KRAS依赖性瘤细胞信号传递和瘤原性活动.
- LPCAT1表达使胰腺癌细胞对KRASG12C抑制剂敏感,并与患者生存率的改善相关.
结论:
- 由LPCAT1重塑的酸 (PS) 酸链选择性地抑制了KRAS瘤发生.
- 对于KRAS突变的癌症来说,LPCAT1是潜在的治疗标.
- 恢复LPCAT1水平可能为克服耐药性和改善KRAS驱动恶性瘤的结果提供了一种策略.
关键词:
克拉斯 (Kras) 是一个国家.Lysophosphatidylcholine 氨基转移酶 1 的作用是什么乙链是一种链.癌症 癌症 癌症 癌症 癌症电子显微镜的电子显微镜纳米集群是指纳米集群.酸盐酸氨酸的含量是多少更多相关视频
相关概念视频
01:20The JAK-STAT Signaling Pathway
8.8K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
8.8K
02:38The Ras Gene
6.2K
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...
Ras is a...
6.2K
01:22Amplifying Signals via Enzymatic Cascade
8.5K
When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
8.5K
01:22PI3K/mTOR/AKT Signaling Pathway
3.5K
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...
3.5K
02:23Abnormal Proliferation
4.5K
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...
4.5K
01:24Small GTPases - Ras and Rho
3.9K
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:
Three regulatory proteins control their activity:
3.9K