Thi Huyen Trang Ha, Hong Suntaek
Department of Biochemistry, Gachon University College of Medicine, Incheon, Korea.
J Cancer Prev. 2017 Jun;22(2):62-73. doi: 10.15430/JCP.2017.22.2.62. Epub 2017 Jun 30.
Chronic inflammation is a critical modulator of carcinogenesis through secretion of inflammatory cytokines, which leads to the formation of an inflammatory microenvironment. In this process, the inflammasome plays an important role in the expression and activation of interleukin (IL)-1β and IL-18 to promote cancer development. The inflammasome is a multiprotein complex consisting of several nucleotide-binding domain and leucine-rich repeat containing receptor, adaptor proteins, and caspase 1 (CASP1). It senses the various intracellular (damage-associated molecular patterns) and extracellular (pathogen-associated molecular patterns) stimuli. A primed inflammasome recruits adaptor proteins, activates CASP1 to enhance the proteolytic cleavage of pro-IL-1β and IL-18, and sends the signal to respond to each insult. Depending on stimuli and cell contexts, several inflammasomes are closely associated with the initiation and promotion of carcinogenesis. In contrast, inflammasomes also show an ambivalent effect on carcinogenesis by enhancing inflammatory cell death (pyroptosis) and repairing damaged tissues. Although the inflammasome plays a controversial role in carcinogenesis, it may be a promising target for human cancer prevention and treatment. A more in-depth study on the role of the inflammasome in carcinogenesis, based on stimuli, cell contexts, and cancer stages, can lead to the development of novel therapeutic strategies against malignant human cancers.
慢性炎症通过分泌炎性细胞因子成为致癌作用的关键调节因子,这会导致炎性微环境的形成。在此过程中,炎性小体在白细胞介素(IL)-1β和IL-18的表达及激活中发挥重要作用,以促进癌症发展。炎性小体是一种多蛋白复合物,由几种含核苷酸结合域和富含亮氨酸重复序列的受体、衔接蛋白以及半胱天冬酶1(CASP1)组成。它能感知各种细胞内(损伤相关分子模式)和细胞外(病原体相关分子模式)刺激。预激活的炎性小体招募衔接蛋白,激活CASP1以增强前体IL-1β和IL-18的蛋白水解切割,并发出信号以应对每种损伤。根据刺激因素和细胞环境,几种炎性小体与癌症发生的起始和促进密切相关。相比之下,炎性小体通过增强炎性细胞死亡(细胞焦亡)和修复受损组织,对癌症发生也表现出矛盾的作用。尽管炎性小体在癌症发生中发挥着有争议的作用,但它可能是人类癌症预防和治疗的一个有前景的靶点。基于刺激因素、细胞环境和癌症阶段,对炎性小体在癌症发生中的作用进行更深入的研究,可能会导致针对人类恶性肿瘤的新型治疗策略的开发。