GPR54通过dopa脱碳酶调节非小细胞肺癌的发展
Hyun-Ha Hwang1, Seo Yeon Lee1, Chanhee Lee2,3
1Department of Science in Korean Medicine, Graduate School, College of Korean Medicine, Kyung Hee University, Seoul, Korea.
Signal transduction and targeted therapy
|March 2, 2026
概括
G蛋白结合受体54 (GPR54) 通过多巴脱碳酶 (DDC) 调节非小细胞肺癌 (NSCLC) 的发展. 准GPR54可能为NSCLC治疗提供新的治疗策略.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 非小细胞肺癌 (NSCLC) 是癌症死亡的主要原因.
- 在NSCLC的发病过程中,G蛋白结合受体54 (GPR54) 的作用尚未完全阐明.
- GPR54与kisspeptin (由KISS1编码) 相互作用,并影响癌症的发展.
研究的目的:
- 研究GPR54在NSCLC发育中的作用.
- 在NSCLC中识别由GPR54调节的下游信号通路.
- 探索GPR54作为NSCLC的诊断标记物和治疗点的潜力.
主要方法:
- 利用一个突变的Kras驱动的小鼠肺癌模型与腺病毒CMV-Cre介导的Gpr54删除.
- 在人类NSCLC细胞系中进行GPR54敲击.
- 采用RNA测序和蛋白阵列来分析信号通路和基因表达.
- 在实验室中评估NSCLC细胞增殖和体内瘤生长.
主要成果:
- 在小鼠和人类的NSCLC细胞中,Gpr54的缺失减弱了NSCLC的发展,并诱导了细胞死亡.
- GPR54信号传递涉及Gαq/11/AKT和β-arrestin/ERK通路,这些通路调节了增殖.
- 通过Gαq/11/PI3K/AKT/mTOR途径,Gpr54的缺失改变了与糖解相关的基因组和调节的Ddc基因表达.
- 多巴脱碳酶 (DDC) 调节NF-κB酸化,影响NSCLC细胞增殖和瘤生长.
结论:
- 在NSCLC的发展和进展中,GPR54起着重要作用.
- GPR54通过DDC影响NSCLC,并影响糖解和NF-κB信号传递.
- GPR54可以作为诊断生物标志物和NSCLC的治疗点.
更多相关视频
06:03Orthotopic Transplantation of Syngeneic Lung Adenocarcinoma Cells to Study PD-L1 Expression
Published on: January 19, 2019
13:18Network Pharmacology Prediction and Experimental Validation of Trichosanthes-Fritillaria thunbergii Action Mechanism Against Lung Adenocarcinoma
Published on: March 3, 2023
相关概念视频
Negative Regulator Molecules
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
Abnormal 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...
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...
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...
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:
Three regulatory proteins control their activity:
GPCRs Regulate Adenylyl Cylase Activity
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...
Two...
