Amara Suneetha, Tiriveedhi Venkataswarup
Department of Medicine, St. Thomas Health Mid-town Hospital, Nashville, TN, USA.
Department of Biological Sciences, Tennessee State University, Nashville, TN, USA.
Int J Oncol. 2017 May;50(5):1477-1481. doi: 10.3892/ijo.2017.3936. Epub 2017 Mar 27.
Chronic inflammation is known to play a critical role in cancer development and progression. High salt is known to mediate several chronic inflammatory diseases including hypertension, myocardial infarction, neurological ischemic attack, autoimmune diseases and cancers. High salt level is shown to induce angiogenesis and immune-dysfunction, both of which play a direct role in cancer proliferation. Furthermore, salt has been suggested to enhance Warburg-like metabolic phenotype in cancer cells and at the same time also induce pro-tumor MΦ2-macrophage phenotype. Recent studies have identified several molecular targets such as tonicity specific transcript factor NFAT5/TonEBP, sodium ion channel γENaC, and vascular endothelial growth factor, VEGF, which are upregulated under high salt external environment. These molecular targets offer futuristic therapeutic application in precision medicine. In this review, we discuss the current understanding of the salt mediated metabolic and immune dysfunctions playing a potential role in cancerous changes.
已知慢性炎症在癌症的发生和发展中起关键作用。已知高盐介导多种慢性炎症性疾病,包括高血压、心肌梗死、神经缺血性发作、自身免疫性疾病和癌症。高盐水平被证明可诱导血管生成和免疫功能障碍,二者在癌症增殖中均起直接作用。此外,有研究表明盐可增强癌细胞中类似瓦伯格效应的代谢表型,同时还可诱导促肿瘤的MΦ2巨噬细胞表型。最近的研究确定了几个分子靶点,如渗透压特异性转录因子NFAT5/TonEBP、钠离子通道γENaC和血管内皮生长因子VEGF,它们在高盐外部环境下上调。这些分子靶点为精准医学提供了未来的治疗应用。在这篇综述中,我们讨论了目前对盐介导的代谢和免疫功能障碍在癌变过程中潜在作用的理解。