SIRT1 suppresses the epithelial-to-mesenchymal transition in cancer metastasis and organ fibrosis.
نویسندگان
چکیده
The epithelial-to-mesenchymal transition (EMT) is important for the development of cancer metastases and organ fibrosis, conditions prevalent in aging. Because sirtuins affect the pathology of aging, we tested the effect of SirT1 on EMT. Reduced SIRT1 levels in HMLER breast cancer cells led to increased metastases in nude mice, and the loss of SIRT1 in kidney tubular epithelial cells exacerbated injury-induced kidney fibrosis. SIRT1 reduces EMT in cancer and fibrosis by deacetylating Smad4 and repressing the effect of TGF-β signaling on MMP7, a Smad4 target gene. Consequently, less E-cadherin is cleaved from the cell surface and β-catenin remains bound to E-cadherin at the cell-cell junctions. Our findings suggest that the SIRT1/Smad4/β-catenin axis may be a target for diseases driven by EMT.
منابع مشابه
Epithelial to mesenchymal transition concept in Cancer: Review article
Owing to this fact that most of the mortalities in cancers are as a result of metastasis, study on the involved pathways in metastasis including Epithelial to mesenchymal transition (EMT) would be so critical and important. Up to date, several extensive studies have been carried out to determine the correlation between EMT and cancer and their results have shown that the EMT plays pivotal role ...
متن کاملAnalysis of epithelial mesenchymal transition markers in breast cancer cells in response to stromal cell-derived factor 1
Introduction: Metastasis is the main cause of cancer death; however, the underlying mechanisms of metastasis are largely unknown. The chemokine of stromal cell-derived factor 1 (SDF1) and the process of epithelial mesenchymal transition (EMT), both have been declared as important factors to promote cancer metastasis; however, Conspicuously, the relation between them has not been recognized well...
متن کاملMesenchymal Stem Cells Trigger Epithelial to Mesenchymal Transition in the HT-29 Colorectal Cancer Cell Line
Background and Objective: Mesenchymal stem cells (MSCs) promote metastasis in colorectal cancer; however, the mechanism underlying this process is not fully understood. Epithelial to mesenchymal transition (EMT) is a key step in tumor acquisition of metastatic phenotype. We aimed to investigate the effect of MSCs on the expression of EMT markers, as well as cancer stem cell markers in HT-29 col...
متن کاملPIASy mediates hypoxia-induced SIRT1 transcriptional repression and epithelial-to-mesenchymal transition in ovarian cancer cells.
Epithelial-mesenchymal transition (EMT) has an essential role in organogenesis and contributes to a host of pathologies, including carcinogenesis. Hypoxia (low oxygen supply) aids tumor metastasis in part by promoting EMT in cancer cells. The underlying mechanism whereby hypoxia orchestrates EMT remains poorly defined. Here we report that SIRT1, a multifaceted player in tumorigenesis, opposed o...
متن کاملNDRG2 Regulates the Expression of Genes Involved in Epithelial Mesenchymal Transition of Prostate Cancer Cells
Background: Metastasis is the main cause of prostate cancer (PCa) death. The inhibitory effect of N-myc downstream-regulated gene 2 (NDRG2) on the invasiveness properties of PCa cells has been demonstrated previously. However, its underlying mechanisms have not yet been investigated. The present study aimed to investigate the effects of NDRG2 overexpression on the expression of genes involved i...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Cell reports
دوره 3 4 شماره
صفحات -
تاریخ انتشار 2013