感官神经CGRP及其共同受体RAMP1驱动胃肠道癌症中的瘤细胞生长
Pavitha Parathan1,2,3, Kelly Tran1,2,3, Liam Neil1,2
1Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia.
BMJ oncology
|October 29, 2025
概括
在胃肠道癌症中的瘤细胞利用神经素素基因相关 (CGRP) 进行生长. 这项研究发现CGRP促进瘤进展,并将瘤细胞确定为CGRP的来源,揭示了新的治疗点.
科学领域:
- 在瘤学瘤学.
- 神经科学是一个神经科学.
- 分子生物学分子生物学
背景情况:
- 胃肠道的神经网络对于肠道功能至关重要.
- 瘤细胞通过与包括神经在内的微环境相互作用来适应,以促进生长.
- 在人类肠道癌症中,瘤细胞与神经的相互作用机制尚不清楚.
研究的目的:
- 研究素基因相关 (CGRP) 和其受体成分受体活性修饰蛋白1 (RAMP1) 在肠道癌症中的表达和功能.
- 阐明癌细胞利用神经质生长的新机制.
- 评估瘤神经轴在胃肠癌进展中的作用.
主要方法:
- 分析了180名患者样本 (结肠直肠癌,CRC肝转移,胃癌,GC) 使用多重免疫组织化学检测CGRP和RAMP1的表达.
- 关联RAMP1表达与患者人口统计学,瘤特征和癌症基因组图谱中的生存数据.
- 通过体外试验和RNA测序,评估CGRP在瘤细胞系和患者衍生器官上的功能.
主要成果:
- 在CRC和GC中,RAMP1表达与降低生存率显著相关.
- 超过50%的CRC和60%的GC细胞表达RAMP1,在微卫星不稳定性 (MSI) 瘤和年轻GC患者中进行丰富.
- 在瘤细胞附近发现并由瘤细胞产生的CGRP以RAMP1依赖的方式增强了瘤细胞的生长,升调了增殖,代谢和迁移的基因.
结论:
- 揭示了肠胃癌中CGRP介导的瘤生长的新机制.
- 瘤细胞被确定为CGRP的来源,扩大了神经参与的知识.
- 瘤神经轴为胃肠道癌症治疗提供了潜在的治疗点.
相关概念视频
mTOR Signaling and Cancer Progression
4.6K
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...
4.6K
Mitogens and the Cell Cycle
7.7K
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...
7.7K
The Ras Gene
7.0K
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...
7.0K
Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists
564
Neurokinin 1 (NK1) receptors are distributed across the GI tract, vagal afferents, and key CNS regions including the central vomiting center and chemoreceptor trigger zone (CTZ) Chemotherapy agents stimulate enterochromaffin cells in the gastrointestinal (GI) tract to release large amounts of substance P (SP). SP is a neuropeptide released by specific sensory nerves in response to many different stressors, including those in the GI mucosa affected by chemotherapy. SP binds and activates...
564
Abnormal Proliferation
5.1K
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...
5.1K
GPCRs Regulate Adenylyl Cylase Activity
7.3K
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...
7.3K


