scholarly journals P-Akt/miR-200 signaling regulates epithelial-mesenchymal transition, migration and invasion in circulating gastric tumor cells

2014 ◽  
Vol 45 (6) ◽  
pp. 2430-2438 ◽  
Author(s):  
DANDAN YUAN ◽  
HONGWEI XIA ◽  
YUCHEN ZHANG ◽  
LIANG CHEN ◽  
WEIBING LENG ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Epithelial Mesenchymal Transition ◽  
Gastric Tumor ◽  
Migration And Invasion ◽  
Mesenchymal Transition

scholarly journals MicroRNAs and Their Influence on the ZEB Family: Mechanistic Aspects and Therapeutic Applications in Cancer Therapy

Biomolecules ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 1040 ◽  
Author(s):  
Milad Ashrafizadeh ◽  
Hui Li Ang ◽  
Ebrahim Rahmani Moghadam ◽  
Shima Mohammadi ◽  
Vahideh Zarrin ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Cancer Therapy ◽  
Signaling Pathways ◽  
Tumor Cells ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Mesenchymal Transition ◽  
The Impact

Molecular signaling pathways involved in cancer have been intensively studied due to their crucial role in cancer cell growth and dissemination. Among them, zinc finger E-box binding homeobox-1 (ZEB1) and -2 (ZEB2) are molecules that play vital roles in signaling pathways to ensure the survival of tumor cells, particularly through enhancing cell proliferation, promoting cell migration and invasion, and triggering drug resistance. Importantly, ZEB proteins are regulated by microRNAs (miRs). In this review, we demonstrate the impact that miRs have on cancer therapy, through their targeting of ZEB proteins. MiRs are able to act as onco-suppressor factors and inhibit the malignancy of tumor cells through ZEB1/2 down-regulation. This can lead to an inhibition of epithelial-mesenchymal transition (EMT) mechanism, therefore reducing metastasis. Additionally, miRs are able to inhibit ZEB1/2-mediated drug resistance and immunosuppression. Additionally, we explore the upstream modulators of miRs such as long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), as these regulators can influence the inhibitory effect of miRs on ZEB proteins and cancer progression.

scholarly journals Breast tumor cell-specific knockout of Twist1 inhibits cancer cell plasticity, dissemination, and lung metastasis in mice

2017 ◽  
Vol 114 (43) ◽  
pp. 11494-11499 ◽  
Author(s):  
Yixiang Xu ◽  
Dong-Kee Lee ◽  
Zhen Feng ◽  
Yan Xu ◽  
Wen Bu ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Tumor Cells ◽  
Lung Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Early Stage ◽  
Migration And Invasion ◽  
Small Subset ◽  
Cell Plasticity ◽  
Mesenchymal Transition

Twist1 is an epithelial–mesenchymal transition (EMT)-inducing transcription factor (TF) that promotes cell migration and invasion. To determine the intrinsic role of Twist1 in EMT and breast cancer initiation, growth, and metastasis, we developed mouse models with an oncogene-induced mammary tumor containing wild-type (WT) Twist1 or tumor cell-specific Twist1 knockout (Twist1TKO). Twist1 knockout showed no effects on tumor initiation and growth. In both models with early-stage tumor cells, Twist1, and mesenchymal markers were not expressed, and lung metastasis was absent. Twist1 expression was detected in ∼6% of the advanced WT tumor cells. Most of these Twist1+ cells coexpressed several other EMT-inducing TFs (Snail, Slug, Zeb2), lost ERα and luminal marker K8, acquired basal cell markers (K5, p63), and exhibited a partial EMT plasticity (E-cadherin+/vimentin+). In advanced Twist1TKO tumor cells, Twist1 knockout largely diminished the expression of the aforementioned EMT-inducing TFs and basal and mesenchymal markers, but maintained the expression of the luminal markers. Circulating tumor cells (CTCs) were commonly detected in mice with advanced WT tumors, but not in mice with advanced Twist1TKO tumors. Nearly all WT CTCs coexpressed Twist1 with other EMT-inducing TFs and both epithelial and mesenchymal markers. Mice with advanced WT tumors developed extensive lung metastasis consisting of luminal tumor cells with silenced Twist1 and mesenchymal marker expression. Mice with advanced Twist1TKO tumors developed very little lung metastasis. Therefore, Twist1 is required for the expression of other EMT-inducing TFs in a small subset of tumor cells. Together, they induce partial EMT, basal-like tumor progression, intravasation, and metastasis.

MicroRNA-483-3p Promotes Proliferation, Migration, and Invasion and Induces Chemoresistance of Wilms’ Tumor Cells

2019 ◽  
Vol 23 (2) ◽  
pp. 144-151 ◽  
Author(s):  
Guanghua Che ◽  
Hang Gao ◽  
Jing Tian ◽  
Qibo Hu ◽  
Hongchang Xie ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Epithelial Mesenchymal Transition ◽  
Wilms Tumor ◽  
Migration And Invasion ◽  
Chemotherapy Response ◽  
Aberrant Expression ◽  
Mesenchymal Transition ◽  
Expression Levels ◽  
Matrigel Invasion ◽  
Induced Apoptosis

Wilms’ tumor is the most common pediatric renal malignancy. MiRNAs are important regulators in multiple cancers including Wilms’ tumor. In this study, we examined the role of miR-483-3p on proliferation, chemosensitivity, migration, and invasion of Wilms’ tumor cells. The proliferation of Wilms’ tumor cells was examined using WST-1 assay. The migration and invasion of Wilms’ tumor cells were evaluated by transwell migration assay and matrigel invasion assay. The protein expression levels were detected by Western blot. The effect of miR-483-3p on doxorubicin-induced apoptosis in Wilms’ tumor cells was evaluated by caspase-Glo3/7 assay. Forced expression of miR-483-3p promoted the proliferation, migration, and invasion in Wilms’ tumor cells. Meanwhile, miR-483-3p decreased the sensitivity of Wilms’ tumor cells after doxorubicin treatment. MiR-483-3p inhibited the doxorubicin-induced apoptosis in Wilms’ tumor cells by the regulation of BAX and Bcl-2 expression. Furthermore, miR-483-3p regulated epithelial–mesenchymal transition by affecting the expression of E-cadherin, N-cadherin, snail, and vimentin in Wilms’ tumor cells. Further studies showed that the expression levels of PTEN and p-AKT in Wilms’ tumor cells were changed after aberrant expression of miR-483-3p by binding to 3′-UTR of PTEN. Our study suggests that miR-483-3p played important roles in proliferation and progression in Wilms’ tumor cells and might serve as a potential prognostic biomarker and predict chemotherapy response in Wilms’ tumor.

scholarly journals Markers of Cancer Cell Invasion: Are They Good Enough?

2019 ◽  
Vol 8 (8) ◽  
pp. 1092 ◽  
Author(s):  
Tatiana S. Gerashchenko ◽  
Nikita M. Novikov ◽  
Nadezhda V. Krakhmal ◽  
Sofia Y. Zolotaryova ◽  
Marina V. Zavyalova ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Cancer Cell ◽  
Cell Invasion ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Cancer Tissue ◽  
Cancer Cell Invasion ◽  
Mesenchymal Transition ◽  
Morphological Heterogeneity ◽  
Extracellular Matrix Components

Invasion, or directed migration of tumor cells into adjacent tissues, is one of the hallmarks of cancer and the first step towards metastasis. Penetrating to adjacent tissues, tumor cells form the so-called invasive front/edge. The cellular plasticity afforded by different kinds of phenotypic transitions (epithelial–mesenchymal, collective–amoeboid, mesenchymal–amoeboid, and vice versa) significantly contributes to the diversity of cancer cell invasion patterns and mechanisms. Nevertheless, despite the advances in the understanding of invasion, it is problematic to identify tumor cells with the motile phenotype in cancer tissue specimens due to the absence of reliable and acceptable molecular markers. In this review, we summarize the current information about molecules such as extracellular matrix components, factors of epithelial–mesenchymal transition, proteases, cell adhesion, and actin cytoskeleton proteins involved in cell migration and invasion that could be used as invasive markers and discuss their advantages and limitations. Based on the reviewed data, we conclude that future studies focused on the identification of specific invasive markers should use new models one of which may be the intratumor morphological heterogeneity in breast cancer reflecting different patterns of cancer cell invasion.

scholarly journals The Vicious Cross-Talk between Tumor Cells with an EMT Phenotype and Cells of the Immune System

Cells ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 460 ◽  
Author(s):  
Elisabetta Romeo ◽  
Carmelo Antonio Caserta ◽  
Cristiano Rumio ◽  
Fabrizio Marcucci
Keyword(s):  
Immune System ◽  
Tumor Cells ◽  
Cross Talk ◽  
Immune Cells ◽  
Epithelial Mesenchymal Transition ◽  
Large Body ◽  
Adaptive Immune System ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Immune Exclusion

Carcinoma cells that undergo an epithelial-mesenchymal transition (EMT) and display a predominantly mesenchymal phenotype (hereafter EMT tumor cells) are associated with immune exclusion and immune deviation in the tumor microenvironment (TME). A large body of evidence has shown that EMT tumor cells and immune cells can reciprocally influence each other, with EMT cells promoting immune exclusion and deviation and immune cells promoting, under certain circumstances, the induction of EMT in tumor cells. This cross-talk between EMT tumor cells and immune cells can occur both between EMT tumor cells and cells of either the native or adaptive immune system. In this article, we review this evidence and the functional consequences of it. We also discuss some recent evidence showing that tumor cells and cells of the immune system respond to similar stimuli, activate the expression of partially overlapping gene sets, and acquire, at least in part, identical functionalities such as migration and invasion. The possible significance of these symmetrical changes in the cross-talk between EMT tumor cells and immune cells is addressed. Eventually, we also discuss possible therapeutic opportunities that may derive from disrupting this cross-talk.

scholarly journals SOCS1 favors the epithelial-mesenchymal transition in melanoma, promotes tumor progression and prevents antitumor immunity by PD-L1 expression

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
R. Berzaghi ◽  
V. S. C. Maia ◽  
F. V. Pereira ◽  
F. M. Melo ◽  
M. S. Guedes ◽  
...  
Keyword(s):  
Growth Factor ◽  
Tumor Cells ◽  
Epithelial Mesenchymal Transition ◽  
Tumor Development ◽  
Growth Factor Receptor ◽  
Melanoma Cells ◽  
Migration And Invasion ◽  
Fibroblast Growth Factor Receptors ◽  
Mesenchymal Transition

Abstract Silencing of SOCS1 protein with shRNAi lentivirus (shR-SOCS1) led to partial reversion of the tumorigenic phenotype of B16F10-Nex2 melanoma cells. SOCS1 silencing inhibited cell migration and invasion as well as in vitro growth by cell cycle arrest at S phase with increased cell size and nuclei. Down-regulation of SOCS1 decreased the expression of epidermal growth factor receptor, Ins-Rα, and fibroblast growth factor receptors. The present work aimed at analyzing the SOCS1 cell signaling and expression of proteins relevant to tumor development. An RNA microarray analysis of B16F10-Nex2 melanoma cells with SOCS1 silenced by shRNAi-SOCS1 was undertaken in comparison with cells transduced with the empty vector. Among 609 differentially expressed genes, c-Kit, Met and EphA3 cytokine/tyrosine-kinase (TK) receptors were down regulated. A significant decrease in the expression of TK receptors, the phosphorylation of mediators of ERK1/2 and p38 pathways and STAT3 (S727) were observed. Subcutaneous immunization with shR-SOCS1-transduced viable tumor cells rendered protection against melanoma in a syngeneic model, with decreased expression of PD-L1 and of matrix metallo-proteinases (MMPs) and CD-10 in those cells. The present work shows the role of SOCS1 in murine melanoma development and the potential of SOCS1-silenced tumor cells in raising an effective anti-melanoma immune response.

scholarly journals Berberine Suppresses EMT in Liver and Gastric Carcinoma Cells through Combination with TGFβR Regulating TGF-β/Smad Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-21
Author(s):  
Haiyan Du ◽  
Jiangyong Gu ◽  
Qin Peng ◽  
Xiaolan Wang ◽  
Lei Liu ◽  
...  
Keyword(s):  
Binding Energy ◽  
Gastric Carcinoma ◽  
Signaling Pathways ◽  
Tumor Cells ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Sequencing Analysis ◽  
Dependent Manner ◽  
Mesenchymal Transition ◽  
Β Receptor

Berberine (BBR), a natural alkaloid derived from Coptis, has anticancer activity. Some researchers have found that it could restrain epithelial-mesenchymal transition (EMT) of melanoma, neuroblastoma, and other tumor cells. However, it is unclear whether BBR can reverse EMT in hepatocellular carcinoma (HCC) and gastric carcinoma (GC). In our study, BBR inhibited the migration and invasion of HepG2, MGC803, and SGC7901 cells in a dose-dependent manner. Transcription sequencing assays showed that Vimentin, MMP, and Smad3 were downregulated, but Smad2, Smad6, TAB2, ZO-1, and claudin 7 were upregulated when treated with BBR. GO Enrichment analysis of KEGG pathway showed that BBR significantly inhibited TGF-β/Smad at 12 h, then, PI3K/Akt and Wnt/β-catenin signaling pathways at 24 h, which were closely related to the proliferation, migration, and EMT. The results of the transcriptome sequencing analysis were verified by Western Blot. It showed that the expression of epithelial marker E-cadherin and ZO-1 remarkably augmented with BBR treatment, as well as declined mesenchymal markers, including N-cadherin and Vimentin, decreased transcription factor Snail and Slug. The effects of BBR were similar to those of the PI3K inhibitor LY294002 and TGF-β receptor inhibitor SB431542. Furthermore, β-catenin and phosphorylation of AKT, Smad2, and Smad3 were changed dose-dependently by BBR treatment, which upregulated p-Smad2 and downregulated the others. Combined with LY or SB, respectively, BBR could enhance the effects of the two inhibitors. Simultaneously, IGF-1 and TGF-β, which is the activator of PI3K/AKT and TGF-β/Smad, respectively, could reverse the anti-EMT effect of BBR. The Molecular Docking results showed BBR had a high affinity with the TGF-β receptor I (TGFβR1), and the binding energy was -7.5 kcal/mol, which is better than the original ligand of TGFβR1. Although the affinity of BBR with TGF-β receptor II (TGFβR2) was lower than the original ligand of TGFβR2, the more considerable negative binding energy (−8.54 kcal/mol) was obtained. BBR upregulated p-Smad2, which was different from other reports, indicating that the function of Smad2 was relatively complex. Combination BBR with SB could enhance the effect of the inhibitor on EMT, and the results indicated that BBR binding to TGFβR was not competitive with SB to TGFβR since different binding amino acid sites. Our experiments demonstrated BBR increased p-Smad2 and decreased p-Smad3 by binding to TGFβR1 and TGβFR2 inhibiting TGF-β/Smad, then, PI3K/AKT and other signaling pathways to restrain EMT, metastasis, and invasion in tumor cells. The effect of BBR was similar on the three tumor cells.

Exosomal MMP-1 transfers metastasis potential in triple-negative breast cancer through PAR1-mediated EMT

2021 ◽  
Author(s):  
Yihui Zhu ◽  
Zhonghua Tao ◽  
Ying Chen ◽  
Shuchen Lin ◽  
Mingyu Zhu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Cells ◽  
Triple Negative Breast Cancer ◽  
Distant Metastasis ◽  
Intercellular Communication ◽  
Triple Negative ◽  
Epithelial Mesenchymal Transition ◽  
Biologically Active ◽  
Migration And Invasion ◽  
Mesenchymal Transition

Abstract Purpose Triple-negative breast cancer (TNBC) is a subtype of breast cancer with high risk of distant metastasis, in which the intercellular communication between tumor cells also plays a role. Exosomes can be released by tumor cells and promote distant metastasis through intercellular communication or changes in tumor microenvironment, it is an optimized transportation facility for biologically active payloads. This was a hypothesis-generating research on role of exosomal payload in TNBC distant metastasis. Methods Exosomes isolated from supernatant of MDA-MB-231 and MDA-MB-231-HM (a highly pulmonary metastatic variant of parental MDA-MB-231 cells) were characterized. Transwell assay, wound healing and CCK-8 assay were employed to explore the effect of exosomal MMP-1 on the metastatic capability of TNBC cells in vitro. Human breast cancer lung metastasis model in nude mice was established to observe the effect of exosomal MMP-1 in vivo. Tissue microarray and blood samples of TNBC patients were applied to analyze the relevance between MMP-1 with metastasis. Results MDA-MB-231-HM cells secrete exosomes enriched MMP-1, which can be taken up and enhance invasion and migration activities of TNBC cells. After ingesting exosomes enriched with MMP-1, cells secrete more MMP-1, which may interact with membrane G protein receptor protease activated receptor 1 (PAR1), thereby initiating epithelial-mesenchymal transition (EMT) to enhance capability of migration and invasion. The expressions of MMP-1 and PAR1 in the metastases of the 231-HM-exo treated mice were both up-regulated. Clinically, the exosomal MMP-1 can be detected from serum of patients with metastasis at higher concentration than that in pre-operative patients. Moreover, in patients with multiple distant metastases, the level of exosomal MMP-1 is also higher than that in patients with single lesion. Conclusion MMP-1 from TNBC cells of high metastasis potential can promote the distant metastasis of transform those with low metastasis potential through PAR1-mediated EMT and is likely to be a potential molecular marker.

scholarly journals Dietary Flavonoids Luteolin and Quercetin Inhibit Migration and Invasion of Squamous Carcinoma through Reduction of Src/Stat3/S100A7 Signaling

Antioxidants ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 557 ◽  
Author(s):  
Jhen-Jia Fan ◽  
Wen-Hsien Hsu ◽  
Kuen-Haur Lee ◽  
Ku-Chung Chen ◽  
Cheng-Wei Lin ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Tumor Cells ◽  
Protein Level ◽  
Calcium Binding ◽  
Epithelial Mesenchymal Transition ◽  
Tumor Formation ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Protein Levels ◽  
Dietary Flavonoids

Flavonoids are well-known antioxidants and have shown the ability to prevent tumor formation and recurrence. Especially in dietary flavonoids, they have provided convenience and consistence of intake for long-term prevention of tumor formation. Previous reports suggested that S100 calcium-binding protein A7 (S100A7) might activate epithelial–mesenchymal transition (EMT) signaling and promote the metastasis of tumor cells; however, the regulatory signaling was unclear. In this study, we found that S100A7 was highly expressed in cancer cells and could be reduced by luteolin (Lu) and quercetin (Qu) through Src/Stat3 signaling. We found that the protein levels of S100A7, phosphorylated Src (p-Src), and p-Stat3 were increased in A431-III cells. Flavonoids Lu and Qu reduce protein levels of p-Src, p-Stat3 and S100A7 in A431-III cells. Treatment of A431-III cells with Src inhibitor SU6656 and Stat3 inhibitor S3I-201 also reduced the protein levels of S100A7. Transactivation activity of 5′-upstream regions of S100A7 was activated by Stat3 but was reduced by treatment with Lu, Qu, SU6656 and S3I-201. The treatment also reduced the migratory and invasive abilities of A431-III cells. In a further analysis of EMT markers, the protein level of E-cad increased and that of Twist decreased after treatment with the inhibitors and flavonoids. Overexpression of S100A7 decreased the protein level of E-cad and increased the Twist level, whereas knockdown of S100A7 had the opposite effects. Treatment with S3I-201, Lu and Qu, compared to the control, were found to decrease metastasis of tumor cells in zebrafish larvae. These results suggest that Lu and Qu may inhibit Src/Stat3/S100A7 signaling to reduce tumorigenesis of cancer cells.

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