scholarly journals SNAIL1: Linking Tumor Metastasis to Immune Evasion

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaolong Tang ◽  
Xue Sui ◽  
Liang Weng ◽  
Yongshuo Liu
Keyword(s):  
Immune Evasion ◽  
Tumor Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Critical Role ◽  
Ubiquitin Proteasome System ◽  
Immune Checkpoints ◽  
Tumor Immune Evasion ◽  
Mesenchymal Transition ◽  
Tumor Immunosuppression ◽  
Immunosuppressive Cells

The transcription factor Snail1, a key inducer of epithelial-mesenchymal transition (EMT), plays a critical role in tumor metastasis. Its stability is strictly controlled by multiple intracellular signal transduction pathways and the ubiquitin-proteasome system (UPS). Increasing evidence indicates that methylation and acetylation of Snail1 also affects tumor metastasis. More importantly, Snail1 is involved in tumor immunosuppression by inducing chemokines and immunosuppressive cells into the tumor microenvironment (TME). In addition, some immune checkpoints potentiate Snail1 expression, such as programmed death ligand 1 (PD-L1) and T cell immunoglobulin 3 (TIM-3). This mini review highlights the pathways and molecules involved in maintenance of Snail1 level and the significance of Snail1 in tumor immune evasion. Due to the crucial role of EMT in tumor metastasis and tumor immunosuppression, comprehensive understanding of Snail1 function may contribute to the development of novel therapeutics for cancer.

scholarly journals miR-612 suppresses the invasive-metastatic cascade in hepatocellular carcinoma

2013 ◽  
Vol 210 (4) ◽  
pp. 789-803 ◽  
Author(s):  
Zhong-Hua Tao ◽  
Jin-Liang Wan ◽  
Ling-Yao Zeng ◽  
Lu Xie ◽  
Hui-Chuan Sun ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Critical Role ◽  
Inhibitory Effects ◽  
Invasion And Metastasis ◽  
Mesenchymal Transition ◽  
Advanced Hcc ◽  
Metastatic Cascade ◽  
First Time

MicroRNAs (miRNAs) play a critical role in tumor metastasis. In this study, we identified a set of 32 miRNAs involved in hepatocellular carcinoma (HCC) metastasis. Among them, miR-612 was shown for the first time to have inhibitory effects on HCC proliferation, migration, invasion, and metastasis. AKT2 was verified to be one of the direct targets of miR-612, through which the epithelial–mesenchymal transition (EMT) and metastasis were inhibited. The level of miR-612 in HCC patients was inversely associated with tumor size, stage, EMT, and metastasis. Of particular importance, miR-612 is involved in both the initial and final steps of the metastatic cascade, by suppressing local invasion and distant colonization. The pleiotropic roles of miR-612 in the HCC metastatic cascade suggest that it could be an effective target for both early and advanced HCC.

scholarly journals Next frontier in tumor immunotherapy: macrophage-mediated immune evasion

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Yingqi Qiu ◽  
Tong Chen ◽  
Rong Hu ◽  
Ruiyi Zhu ◽  
Chujun Li ◽  
...  
Keyword(s):  
Immune Evasion ◽  
Immune Escape ◽  
Tumor Immunotherapy ◽  
Immune Checkpoints ◽  
Cancer Treatments ◽  
Tumor Immune Escape ◽  
Tumor Immune Evasion ◽  
New Ideas ◽  
And Function ◽  
Immunosuppressive Cells

AbstractTumor-associated macrophages (TAMs), at the core of immunosuppressive cells and cytokines networks, play a crucial role in tumor immune evasion. Increasing evidences suggest that potential mechanisms of macrophage-mediated tumor immune escape imply interpretation and breakthrough to bottleneck of current tumor immunotherapy. Therefore, it is pivotal to understand the interactions between macrophages and other immune cells and factors for enhancing existing anti-cancer treatments. In this review, we focus on the specific signaling pathways through which TAMs involve in tumor antigen recognition disorders, recruitment and function of immunosuppressive cells, secretion of immunosuppressive cytokines, crosstalk with immune checkpoints and formation of immune privileged sites. Furthermore, we summarize correlative pre-clinical and clinical studies to provide new ideas for immunotherapy. From our perspective, macrophage-targeted therapy is expected to be the next frontier of cancer immunotherapy.

scholarly journals Silence of Hippo Pathway Associates with Pro-Tumoral Immunosuppression: Potential Therapeutic Target of Glioblastomas

Cells ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1761
Author(s):  
Eui Hyun Kim ◽  
Bo Hwa Sohn ◽  
Young-Gyu Eun ◽  
Dong Jin Lee ◽  
Sun Young Yim ◽  
...  
Keyword(s):  
Poor Prognosis ◽  
Epithelial Mesenchymal Transition ◽  
Hippo Pathway ◽  
Critical Role ◽  
Gene Expression Signature ◽  
Core Gene ◽  
The Cancer Genome Atlas ◽  
Immune Checkpoints ◽  
Mesenchymal Transition ◽  
The Hippo Pathway

The critical role of the Hippo pathway has been recently investigated in various cancers, but little is known about its role in glioblastoma (GBM). In order to evaluate the clinical relevance of the Hippo pathway in GBM, we generated a core gene expression signature from four different previously-established silence of Hippo pathway (SOH) signatures. Based on a newly generated core SOH signature, a SOH and active Hippo pathway (AH) was predicted in GBM samples from The Cancer Genome Atlas (TCGA) and validated in a separate cohort. A comparative analysis was performed on multi-panel genomic datasets from TCGA and the possible association of SOH with immune activity and epithelial mesenchymal transition was also evaluated. The SOH signature was associated with poor prognosis in GBM in both cohorts. Expression levels of CTGF and CYR61, the most reliable and well-known downstream targets of YAP1, were markedly increased in the SOH subgroup of GBM patients. SOH signature was strongly associated with a high immune signature score and mesenchymal features. Genes differentially expressed between SOH and AH groups revealed many markers for inhibitory immune checkpoints and M2-polarized macrophages were upregulated in the SOH subgroup, suggesting that SOH may induce the resistance of cancer cells to host immune response in GBM. In summary, SOH is significantly associated with the poor prognosis of GBM patients and is possibly mediated by pro-tumoral immunosuppression.

scholarly journals Phosphorylation of Serine 11 and Serine 92 as New Positive Regulators of Human Snail1 Function: Potential Involvement of Casein Kinase-2 and the cAMP-activated Kinase Protein Kinase A

2010 ◽  
Vol 21 (2) ◽  
pp. 244-253 ◽  
Author(s):  
Matthew Reid MacPherson ◽  
Patricia Molina ◽  
Serhiy Souchelnytskyi ◽  
Christer Wernstedt ◽  
Jorge Martin-Pérez ◽  
...  
Keyword(s):  
Nuclear Export ◽  
Tumor Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Cop9 Signalosome ◽  
Mesenchymal Transition ◽  
Depth Analysis ◽  
Positive Regulators

Snail1 is a major factor for epithelial-mesenchymal transition (EMT), an important event in tumor metastasis and in other pathologies. Snail1 is tightly regulated at transcriptional and posttranscriptional levels. Control of Snail1 protein stability and nuclear export by GSK3β phosphorylation is important for Snail1 functionality. Stabilization mechanisms independent of GSK3β have also been reported, including interaction with LOXL2 or regulation of the COP9 signalosome by inflammatory signals. To get further insights into the role of Snail1 phosphorylation, we have performed an in-depth analysis of in vivo human Snail1 phosphorylation combined with mutational studies. We identify new phosphorylation sites at serines 11, 82, and 92 and confirmed previously suggested phosphorylations at serine 104 and 107. Serines 11 and 92 participate in the control of Snail1 stability and positively regulate Snail1 repressive function and its interaction with mSin3A corepressor. Furthermore, serines 11 and 92 are required for Snail1-mediated EMT and cell viability, respectively. PKA and CK2 have been characterized as the main kinases responsible for in vitro Snail1 phosphorylation at serine 11 and 92, respectively. These results highlight serines 11 and 92 as new players in Snail1 regulation and suggest the participation of CK2 and PKA in the modulation of Snail1 functionality.

scholarly journals Epithelial–mesenchymal transition in tumor metastasis: a method to the madness

2009 ◽  
Vol 5 (8) ◽  
pp. 1109-1111 ◽  
Author(s):  
Venkateshwar G Keshamouni ◽  
William P Schiemann
Keyword(s):  
Tumor Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition

Carboxypeptidase E-ΔN promotes migration, invasiveness, and epithelial–mesenchymal transition of human osteosarcoma cells via the Wnt–β-catenin pathway

2019 ◽  
Vol 97 (4) ◽  
pp. 446-453 ◽  
Author(s):  
Shuli Fan ◽  
Xiang Gao ◽  
Peng Chen ◽  
Xu Li
Keyword(s):  
Cell Migration ◽  
Tumor Metastasis ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Human Osteosarcoma ◽  
Carboxypeptidase E ◽  
Human Osteosarcoma Cells ◽  
Cancer Types ◽  
Interfering Rna

Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents, and metastatic OS is the major cause of OS-related death. Carboxypeptidase E (CPE) is known to be highly expressed in some cancer types, and its N-terminal truncated form, CPE-ΔN, is implicated in tumor metastasis and poor prognosis. In this study, we investigated the effect of CPE-ΔN on cell migration, invasiveness, and the epithelial–mesenchymal transition (EMT) of OS cells, and illustrated the molecular mechanisms. We first constructed CPE-ΔN overexpressing human OS cell lines (143B and U2OS cells), and found that ectopic CPE-ΔN expression in OS cells enhanced cell migration and invasiveness, and promoted the EMT process. Further, overexpression of CPE-ΔN increased the levels of c-myc and nuclear β-catenin in OS cells, which suggested the CPE-ΔN promotes activation of the Wnt–β-catenin pathway in OS cells. Treatment with β-catenin small interfering RNA (siRNA) inhibited the migration and invasiveness of CPE-ΔN-overexpressing cells, and reduced the expression of E-cadherin. Together, these results suggest that CPE-ΔN promotes migration, invasiveness, and the EMT of OS cells via the Wnt–β-catenin signaling pathway.

scholarly journals Epigenetic silencing of CDKN1A and CDKN2B by SNHG1 promotes the cell cycle, migration and epithelial-mesenchymal transition progression of hepatocellular carcinoma

2020 ◽  
Vol 11 (10) ◽  
Author(s):  
Bei Li ◽  
Ang Li ◽  
Zhen You ◽  
Jingchang Xu ◽  
Sha Zhu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Epithelial Mesenchymal Transition ◽  
Critical Role ◽  
Luciferase Assay ◽  
Bioinformatics Analyses ◽  
Mesenchymal Transition ◽  
Rna Immunoprecipitation

Abstract Enhanced SNHG1 (small nucleolar RNA host gene 1) expression has been found to play a critical role in the initiation and progression of hepatocellular carcinoma (HCC) with its detailed mechanism largely unknown. In this study, we show that SNHG1 promotes the HCC progression through epigenetically silencing CDKN1A and CDKN2B in the nucleus, and competing with CDK4 mRNA for binding miR-140-5p in the cytoplasm. Using bioinformatics analyses, we found hepatocarcinogenesis is particularly associated with dysregulated expression of SNHG1 and activation of the cell cycle pathway. SNHG1 was upregulated in HCC tissues and cells, and its knockdown significantly inhibited HCC cell cycle, growth, metastasis, and epithelial–mesenchymal transition (EMT) both in vitro and in vivo. Chromatin immunoprecipitation and RNA immunoprecipitation assays demonstrate that SNHG1 inhibit the transcription of CDKN1A and CDKN2B through enhancing EZH2 mediated-H3K27me3 in the promoter of CDKN1A and CDKN2B, thus resulting in the de-repression of the cell cycle. Dual-luciferase assay and RNA pulldown revealed that SNHG1 promotes the expression of CDK4 by competitively binding to miR-140-5p. In conclusion, we propose that SNHG1 formed a regulatory network to confer an oncogenic function in HCC and SNHG1 may serve as a potential target for HCC diagnosis and treatment.

The Role of Calcium Signaling in Regulation of Epithelial-Mesenchymal Transition

2020 ◽  
pp. 1-23
Author(s):  
Divya Adiga ◽  
Raghu Radhakrishnan ◽  
Sanjiban Chakrabarty ◽  
Prashant Kumar ◽  
Shama Prasada Kabekkodu
Keyword(s):  
Cancer Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
Epithelial Mesenchymal Transition ◽  
Critical Role ◽  
Cancer Therapeutics ◽  
Growth And Survival ◽  
Mesenchymal Transition ◽  
Microenvironmental Factors ◽  
Favorable Clinical Outcome

Despite substantial advances in the field of cancer therapeutics, metastasis is a significant challenge for a favorable clinical outcome. Epithelial to mesenchymal transition (EMT) is a process of acquiring increased motility, invasiveness, and therapeutic resistance by cancer cells for their sustained growth and survival. A plethora of intrinsic mechanisms and extrinsic microenvironmental factors drive the process of cancer metastasis. Calcium (Ca<sup>2+</sup>) signaling plays a critical role in dictating the adaptive metastatic cell behavior comprising of cell migration, invasion, angiogenesis, and intravasation. By modulating EMT, Ca<sup>2+</sup> signaling can regulate the complexity and dynamics of events leading to metastasis. This review summarizes the role of Ca<sup>2+</sup> signal remodeling in the regulation of EMT and metastasis in cancer.

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