Differential Actions of Muscarinic Receptor Subtypes in Gastric, Pancreatic, and Colon Cancer.
Differential Actions of Muscarinic Receptor Subtypes in Gastric, Pancreatic, and Colon Cancer.
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DOI：
10.3390/ijms222313153
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发表时间：
2021-12-05
影响因子：
5.6
通讯作者：
Raufman JP
中科院分区：
文献类型：
--
作者：
Schledwitz A;Sundel MH;Alizadeh M;Hu S;Xie G;Raufman JP
由胃肠道上皮细胞引起的癌症很常见，侵袭性很强，很难治疗。这一领域的进展源于认识到这些癌症的生物学行为高度依赖于肿瘤微环境中的神经分泌、旁分泌和自分泌机制释放的生物活性分子。在被发现为神经递质后的几十年里，乙酰胆碱被认为是从神经元合成和释放的唯一生理配体，并被认为是具有相似或多余作用的M受体亚型的唯一生理配体。在其间的几年里，我们认识到，以前的教条是站不住脚的。(1)乙酰胆碱不是只由神经元产生和释放的。合成和释放乙酰胆碱所需的细胞机制存在于免疫细胞、癌症细胞和其他细胞中，以及居住在肠道中的低等生物(如细菌)中。(2)乙酰胆碱不是M受体的唯一生理激活剂。例如，选定的胆汁酸可以调节M受体的功能。(3)基于相似的G蛋白偶联和下游信号，预期具有重叠功能的M受体亚型可能具有出人意料的不同作用。在这里，我们回顾支持这些结论的相关研究结果，并讨论M受体生物学的复杂性如何影响健康和疾病，重点讨论它们在胃癌、胰腺癌和结肠癌的发生和发展中的作用。
Cancers arising from gastrointestinal epithelial cells are common, aggressive, and difficult to treat. Progress in this area resulted from recognizing that the biological behavior of these cancers is highly dependent on bioactive molecules released by neurocrine, paracrine, and autocrine mechanisms within the tumor microenvironment. For many decades after its discovery as a neurotransmitter, acetylcholine was thought to be synthesized and released uniquely from neurons and considered the sole physiological ligand for muscarinic receptor subtypes, which were believed to have similar or redundant actions. In the intervening years, we learned this former dogma is not tenable. (1) Acetylcholine is not produced and released only by neurons. The cellular machinery required to synthesize and release acetylcholine is present in immune, cancer, and other cells, as well as in lower organisms (e.g., bacteria) that inhabit the gut. (2) Acetylcholine is not the sole physiological activator of muscarinic receptors. For example, selected bile acids can modulate muscarinic receptor function. (3) Muscarinic receptor subtypes anticipated to have overlapping functions based on similar G protein coupling and downstream signaling may have unexpectedly diverse actions. Here, we review the relevant research findings supporting these conclusions and discuss how the complexity of muscarinic receptor biology impacts health and disease, focusing on their role in the initiation and progression of gastric, pancreatic, and colon cancers.
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DOI：
10.1056/nejmoa2017015
发表时间：
2021-02-25
期刊：
The New England journal of medicine
影响因子：
--
作者：
Brannan SK;Sawchak S;Miller AC;Lieberman JA;Paul SM;Breier A
通讯作者：
Breier A
影响因子：
16.2
作者：
Foster, Daniel J.;Wilson, Jermaine M.;Conn, P. Jeffrey
通讯作者：
Conn, P. Jeffrey
影响因子：
--
作者：
Castro JM;Resende RR;Mirotti L;Florsheim E;Albuquerque LL;Lino-dos-Santos-Franco A;Gomes E;de Lima WT;de Franco M;Ribeiro OG;Russo M
通讯作者：
Russo M
影响因子：
--
作者：
Cheng K;Metry M;Felton J;Shang AC;Drachenberg CB;Xu S;Zhan M;Schumacher J;Guo GL;Polli JE;Raufman JP
通讯作者：
Raufman JP
影响因子：
25
作者：
Anagnostaras, SG;Murphy, GG;Silva, AJ
通讯作者：
Silva, AJ