Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
J Cell Physiol. 2018 Jun;233(6):4443-4457. doi: 10.1002/jcp.26302. Epub 2018 Jan 15.
The epithelial-mesenchymal transition (EMT) is a highly networked cellular process which involves cell transition from the immotile epithelial to the motile mesenchymal phenotype, whereby cells lose their cell-cell adhesion and cell polarity. This important process is one of the underlying mechanisms for enabling invasion and metastasis of cancer cells which is considered as malignant phase of tumor progression. However, the molecular mechanisms of this process are not fully clarified. It is reported that Sirtuin1 (SIRT1), a NAD+ dependent class III histone deacetylase is associated with tumor metastasis through positive regulation of EMT in several types of cancers. Recent studies confirmed that up and down regulation of SIRT1 expression remarkably change the migration ability of different cancer cells in vitro and tumor metastasis in vivo. Also, according to this fact that carcinomas as the main human solid tumors, originate from different epithelial cell types, SIRT1 role in EMT has received a great attention due to its potential role in tumor development and metastasis. Therefore, SIRT1 has been proposed as a key regulator of cancer metastasis by promoting EMT, although little is known about the cleared effect of SIRT1 in this transition. Our aim in this review is to explain in more detail the role of SIRT1 in various signaling pathways related to carcinogenesis, with the focus on the promoting role of SIRT1 in EMT as a potential therapeutic target to control EMT and to prevent cancer progression.
上皮-间充质转化(EMT)是一个高度网络化的细胞过程,涉及细胞从非运动的上皮向运动的间充质表型的转变,在此过程中,细胞失去细胞间的黏附性和细胞极性。这个重要的过程是癌细胞侵袭和转移的潜在机制之一,被认为是肿瘤进展的恶性阶段。然而,这个过程的分子机制尚未完全阐明。有报道称,Sirtuin1(SIRT1)是一种 NAD+依赖性 III 类组蛋白去乙酰化酶,通过正向调控几种类型癌症中的 EMT 与肿瘤转移有关。最近的研究证实,SIRT1 表达的上调和下调显著改变了不同癌细胞在体外的迁移能力和体内的肿瘤转移。此外,由于 SIRT1 在肿瘤发生和转移中的潜在作用,癌作为人类主要的实体瘤,起源于不同的上皮细胞类型,因此 SIRT1 在 EMT 中的作用受到了极大的关注。因此,SIRT1 被认为是促进 EMT 的癌症转移的关键调节剂,尽管人们对 SIRT1 在这种转化中的明确作用知之甚少。我们在这篇综述中的目的是更详细地解释 SIRT1 在与癌变相关的各种信号通路中的作用,重点是 SIRT1 在 EMT 中的促进作用,作为控制 EMT 和预防癌症进展的潜在治疗靶点。