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激肽介导事件在癌症进展和治疗应用中的概述。

An overview of kinin mediated events in cancer progression and therapeutic applications.

机构信息

School of Medical Science & Technology, Indian Institute of Technology Kharagpur, Kharagpur 721302, West Bengal, India.

出版信息

Biochim Biophys Acta Rev Cancer. 2022 Nov;1877(6):188807. doi: 10.1016/j.bbcan.2022.188807. Epub 2022 Sep 24.

Abstract

Kinins are bioactive peptides generated in the inflammatory milieu of the tissue microenvironment, which is involved in cancer progression and inflammatory response. Kinins signals through activation of two G-protein coupled receptors; inducible Bradykinin Receptor B1 (B1R) and constitutive receptor B2 (B2R). Activation of kinin receptors and its cross-talk with receptor tyrosine kinases activates multiple signaling pathways, including ERK/MAPK, PI3K, PKC, and p38 pathways regulating cancer hallmarks. Perturbations of the kinin-mediated events are implicated in various aspects of cancer invasion, matrix remodeling, and metastasis. In the tumor microenvironment, kinins initiate fibroblast activation, mesenchymal stem cell interactions, and recruitment of immune cells. Albeit the precise nature of kinin function in the metastasis and tumor microenvironment are not completely clear yet, several kinin receptor antagonists show anti-metastatic potential. Here, we showcase an overview of the complex biology of kinins and their role in cancer pathogenesis and therapeutic aspects.

摘要

激肽是在组织微环境的炎症环境中产生的生物活性肽,参与癌症的进展和炎症反应。激肽通过两种 G 蛋白偶联受体的激活来传递信号;诱导型缓激肽受体 B1(B1R)和组成型受体 B2(B2R)。激肽受体的激活及其与受体酪氨酸激酶的相互作用激活了多种信号通路,包括 ERK/MAPK、PI3K、PKC 和 p38 通路,调节癌症的标志性特征。激肽介导的事件的紊乱与癌症侵袭、基质重塑和转移的各个方面有关。在肿瘤微环境中,激肽启动成纤维细胞的激活、间充质干细胞的相互作用以及免疫细胞的募集。尽管激肽在转移和肿瘤微环境中的确切功能尚不完全清楚,但几种激肽受体拮抗剂显示出抗转移的潜力。在这里,我们展示了激肽的复杂生物学及其在癌症发病机制和治疗方面的作用概述。

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