Epigenetic Regulation and Post-Translational Modifications of SNAI1 in Cancer Metastasis

Dong, Bo; Wu, Yadi

doi:10.3390/ijms222011062

Cited by 25 publications

(16 citation statements)

References 104 publications

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“…Through EMT induction, epithelial cells undergo cytoskeletal reorganization, engage in extracellular matrix (ECM) remodeling, and become more mobile and invasive, detaching from surrounding cells and the ECM ( 20 ). These changes coincide with a reduction in the expression of epithelial marker proteins and the upregulation of mesenchymal marker proteins including Vimentin and N-cadherin, with this process being regulated by key transcription factors including members of the TWIST, SNAIL, and ZEB families ( 21 , 22 ). Prior studies have shown ECM1 to play a role in this EMT process in several epithelial malignancies, thereby promoting metastatic progression.…”

Section: Discusionmentioning

confidence: 97%

Extracellular Matrix Protein 1 Regulates Colorectal Cancer Cell Proliferative, Migratory, Invasive and Epithelial-Mesenchymal Transition Activities Through the PI3K/AKT/GSK3β/Snail Signaling Axis

et al. 2022

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In prior reports, extracellular matrix protein 1 (ECM1) upregulation has been reported in colorectal cancer (CRC) patient tumor tissues, and has been suggested to be related to the metastatic progression of CRC, although the underlying mechanisms have yet to be clarified. In this study, we found that ECM1 was overexpressed in both CRC tissues and cell lines. Upregulation of ECM1 was correlated with tumor size, lymph node status and TNM stage in CRC patients. Knocking down ECM1 suppressed CRC cell growth, migration and invasion, in addition to reducing the expression of Vimentin and increasing E-cadherin expression. The overexpression of ECM1, in contrast, yielded the opposite phenotypic outcomes while also promoting the expression of p-AKT, p-GSK3β, and Snail, which were downregulated when ECM1 was knocked down. Treatment with LY294002 and 740 Y-P reversed the impact upregulation and downregulation of ECM1 on CRC cell metastasis and associated EMT induction. In vivo analyses confirmed that ECM1 overexpression was able to enhance EMT induction and CRC tumor progression. In conclusion, ECM1 influences CRC development and progression in an oncogenic manner, and regulates CRC metastasis and EMT processes via the PI3K/AKT/GSK3β/Snail signaling axis.

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Section: Discusionmentioning

confidence: 97%

Extracellular Matrix Protein 1 Regulates Colorectal Cancer Cell Proliferative, Migratory, Invasive and Epithelial-Mesenchymal Transition Activities Through the PI3K/AKT/GSK3β/Snail Signaling Axis

et al. 2022

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“…Similarly, in the current investigation, gene expression of SMAD3 and SMAD4 was significantly reduced in the tumours of the patients with underlying COPD. This signalling pathway may play an important role in the initiation of a profibrogenic effect through TGF-β signalling in patients with COPD, thus favouring lung carcinogenesis [ 12 , 27 ]. As such the downregulation of the EMT repressor SMAD pathway may favour a pro-tumoural micro-environment in patients with chronic airways diseases, namely COPD, which could be targeted therapeutically.…”

Section: Discussionmentioning

confidence: 99%

“…Epithelial–mesenchymal transition (EMT) is a biological process characterised by the loss of polarity and cell–cell adhesion of epithelial cells to gain invasive characteristics. The transformed epithelial cells become mesenchymal stem cells, which can differentiate into a great variety of cell types [ 11 , 12 ]. EMT is a physiological process involved in organ development in the embryo and in wounds [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Gene expression profile of epithelial–mesenchymal transition in tumours of patients with nonsmall cell lung cancer: the influence of COPD

et al. 2022

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Epithelial-mesenchymal transition (EMT) is involved in the pathophysiology of lung cancer (LC) and chronic obstructive pulmonary disease (COPD), and the latter is an important risk factor for LC. We hypothesized that gene expression profile of EMT and signaling cascade may differ in LC patients with COPD from those with no respiratory diseases. In lung tumor specimens obtained through video-assisted thoracoscopic surgery (VATS) from LC (n=20, control group) and LC-COPD patients (n=30), gene expression (qRT-PCR) of EMT markers: SMAD3, SMAD4, ZEB2, TWIST1, SNAI1, ICAM1, VIM, CDH2, MMP1, and MMP9 were detected. In lung tumors of LC-COPD compared to LC patients, gene expression of SMAD3, SMAD4, ZEB2, and CDH2 significantly declined, while no significant differences were detected for the other analyzed markers. A significant correlation was found between packs-years (smoking burden) and SMAD3 gene expression among LC-COPD patients. LC-COPD patients exhibited mild-to-moderate airway obstruction and a significant reduction in diffusion capacity compared to LC patients. In lung tumor samples of patients with COPD, several markers of EMT expression, namely SMAD3, SMAD4, ZEB2, and CDH2 were differentially expressed suggesting that these markers are likely to play a role in the regulation of EMT in patients with this respiratory disease. Cigarette smoke did not seem to influence the expression of EMT markers in this study. These results have potential clinical implications in the management of patients with LC, particularly in those with underlying respiratory diseases.

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“…Since then, the list of TFs has been updated, and new findings in the complex regulatory network they form were recently summarized (Debnath et al, 2022). Regarding Snail-1, the involvement of the B-Raf proto-oncogene (BRAF) gene was highlighted, linked with chemoresistance in thyroid cancer (Wieczorek-Szukala and Lewinski, 2021), and the role of epigenetic regulation was emphasized (Dong and Wu, 2021). Even more important, Snail-1 was shown to be involved in tumor immunosuppression by inducing chemokines and immunosuppressive cells into the tumor microenvironment (Tang et al, 2021).…”

Section: Transcriptional and Translation Factorsmentioning

confidence: 99%

Curcuminoids as Modulators of EMT in Invasive Cancers: A Review of Molecular Targets With the Contribution of Malignant Mesothelioma Studies

et al. 2022

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Curcuminoids, which include natural acyclic diarylheptanoids and the synthetic analogs of curcumin, have considerable potential for fighting against all the characteristics of invasive cancers. The epithelial-to-mesenchymal transition (EMT) is a fundamental process for embryonic morphogenesis, however, the last decade has confirmed it orchestrates many features of cancer invasiveness, such as tumor cell stemness, metabolic rewiring, and drug resistance. A wealth of studies has revealed EMT in cancer is in fact driven by an increasing number of parameters, and thus understanding its complexity has now become a cornerstone for defining future therapeutic strategies dealing with cancer progression and metastasis. A specificity of curcuminoids is their ability to target multiple molecular targets, modulate several signaling pathways, modify tumor microenvironments and enhance the host’s immune response. Although the effects of curcumin on these various parameters have been the subject of many reviews, the role of curcuminoids against EMT in the context of cancer have never been reviewed so far. This review first provides an updated overview of all EMT drivers, including signaling pathways, transcription factors, non-coding RNAs (ncRNAs) and tumor microenvironment components, with a special focus on the most recent findings. Secondly, for each of these drivers the effects of curcumin/curcuminoids on specific molecular targets are analyzed. Finally, we address some common findings observed between data reported in the literature and the results of investigations we conducted on experimental malignant mesothelioma, a model of invasive cancer representing a useful tool for studies on EMT and cancer.

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Epigenetic Regulation and Post-Translational Modifications of SNAI1 in Cancer Metastasis

Cited by 25 publications

References 104 publications

Extracellular Matrix Protein 1 Regulates Colorectal Cancer Cell Proliferative, Migratory, Invasive and Epithelial-Mesenchymal Transition Activities Through the PI3K/AKT/GSK3β/Snail Signaling Axis

Extracellular Matrix Protein 1 Regulates Colorectal Cancer Cell Proliferative, Migratory, Invasive and Epithelial-Mesenchymal Transition Activities Through the PI3K/AKT/GSK3β/Snail Signaling Axis

Gene expression profile of epithelial–mesenchymal transition in tumours of patients with nonsmall cell lung cancer: the influence of COPD

Curcuminoids as Modulators of EMT in Invasive Cancers: A Review of Molecular Targets With the Contribution of Malignant Mesothelioma Studies

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