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受体-配体相互作用在生长抑素信号通路中的作用:对神经内分泌肿瘤的影响

The Role of Receptor-Ligand Interaction in Somatostatin Signaling Pathways: Implications for Neuroendocrine Tumors.

作者信息

Milewska-Kranc Agnieszka, Ćwikła Jarosław B, Kolasinska-Ćwikła Agnieszka

机构信息

GENELYTICA Sp. z o.o., Akademicka 48a, 18-400 Łomża, Poland.

School of Medicine, University of Warmia and Mazury, Aleja Warszawska 30, 10-082 Olsztyn, Poland.

出版信息

Cancers (Basel). 2023 Dec 25;16(1):116. doi: 10.3390/cancers16010116.

Abstract

Neuroendocrine tumors (NETs) arise from neuroendocrine cells and manifest in diverse organs. Key players in their regulation are somatostatin and its receptors (SSTR1-SSTR5). Understanding receptor-ligand interactions and signaling pathways is vital for elucidating their role in tumor development and therapeutic potential. This review highlights SSTR characteristics, localization, and expression in tissues, impacting physiological functions. Mechanisms of somatostatin and synthetic analogue binding to SSTRs, their selectivity, and their affinity were analyzed. Upon activation, somatostatin initiates intricate intracellular signaling, involving cAMP, PLC, and MAP kinases and influencing growth, differentiation, survival, and hormone secretion in NETs. This review explores SSTR expression in different tumor types, examining receptor activation effects on cancer cells. SSTRs' significance as therapeutic targets is discussed. Additionally, somatostatin and analogues' role in hormone secretion regulation, tumor growth, and survival is emphasized, presenting relevant therapeutic examples. In conclusion, this review advances the knowledge of receptor-ligand interactions and signaling pathways in somatostatin receptors, with potential for improved neuroendocrine tumor treatments.

摘要

神经内分泌肿瘤(NETs)起源于神经内分泌细胞,可在多种器官中表现出来。其调节的关键因素是生长抑素及其受体(SSTR1 - SSTR5)。了解受体 - 配体相互作用和信号通路对于阐明它们在肿瘤发展中的作用和治疗潜力至关重要。本综述重点介绍了SSTR的特性、在组织中的定位和表达,及其对生理功能的影响。分析了生长抑素和合成类似物与SSTRs结合的机制、它们的选择性和亲和力。激活后,生长抑素启动复杂的细胞内信号传导,涉及cAMP、PLC和MAP激酶,并影响NETs中的生长、分化、存活和激素分泌。本综述探讨了SSTR在不同肿瘤类型中的表达,研究了受体激活对癌细胞的影响。讨论了SSTR作为治疗靶点的意义。此外,强调了生长抑素及其类似物在激素分泌调节、肿瘤生长和存活中的作用,并列举了相关治疗实例。总之,本综述推进了对生长抑素受体中受体 - 配体相互作用和信号通路的认识,具有改善神经内分泌肿瘤治疗的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d03b/10778465/f6d193c03ad2/cancers-16-00116-g001.jpg

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