scholarly journals CXCL14 facilitates the growth and metastasis of ovarian carcinoma cells via activation of the Wnt/β-catenin signaling pathway

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Li-Na Gao ◽  
Man Hao ◽  
Xiao-Hui Liu ◽  
Li Zhang ◽  
Yan Dong ◽  
...  
Keyword(s):  
Cell Growth ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Mrna Level ◽  
Metastatic Potential ◽  
Migration And Invasion ◽  
Migration Ability ◽  
Mesenchymal Transition

Abstract Background There is an urgent need to identify potential targets in anticancer therapy to improve the survival and prognosis of patients with ovarian cancer (OC). Herein, we investigated the functional significance of chemokine (C-X-C motif) ligand 14 (CXCL14) in OC cell growth and epithelial–mesenchymal transition (EMT). Methods qRT PCR and western blotting was used to detect CXCL14 mRNA level and protein expression, respectively. The functional mechanism of CXCL14 in OC was investigated by CCK-8, colony formation and transwell assays. The migration ability of OC cell was determined using wound healing. The protein expressions of CXCL14 and β-catenin in OC tissues were determined by immumohistochemical staining. Results We demonstrated that high levels of CXCL14 were associated with a worse prognosis in patients with OC. CXCL14 knockdown considerably restrained the growth, migration and invasion of OC cell in vitro. In contrast, ectopic CXCL14 overexpression yielded the opposite results. Investigations to determine the underlying molecular mechanisms revealed that the Wnt/β-catenin signaling pathway is involved in CXCL14-facilitated OC cell invasiveness. Conclusion These data collectively demonstrate that CXCL14 contributes to OC cell growth and metastatic potential by regulating the Wnt/β-catenin signaling pathway.

scholarly journals CXCL14 Facilitates the Growth and Metastasis of Ovarian Carcinoma Cells via Activation of the Wnt/β-catenin Signaling Pathway

2021 ◽  
Author(s):  
Li-Na Gao ◽  
Man Hao ◽  
Xiao-Hui Liu ◽  
Li Zhang ◽  
Yan Dong ◽  
...  
Keyword(s):  
Cell Growth ◽  
Protein Expression ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Mrna Level ◽  
Metastatic Potential ◽  
Mesenchymal Transition ◽  
Cell Invasiveness

Abstract Background There is an urgent need to identify potential targets in anticancer therapy to improve the survival and prognosis of patients with ovarian cancer (OC). Herein, we investigated the functional significance of chemokine (C-X-C motif) ligand 14 (CXCL14) in OC cell growth and epithelial–mesenchymal transition (EMT).MethodsqRT PCR and western blotting was used to detect CXCL14 mRNA level and protein expression, respectively. The functional mechanism of CXCL14 in OC was investigated by CCK-8, colony formation and transwell assays. The protein expression of CXCL14 and β-catenin in OC tissues was determined by immumohistochemical staining.ResultsWe demonstrated that high levels of CXCL14 were associated with a worse prognosis in patients with OC. CXCL14 knockdown considerably restrained the growth and invasion of OC cells in vitro. In contrast, ectopic CXCL14 overexpression yielded the opposite results. Investigations to determine the underlying molecular mechanisms revealed that the Wnt/β-catenin signaling pathway is involved in CXCL14-facilitated OC cell invasiveness.ConclusionThese data collectively demonstrate that CXCL14 contributes to OC cell growth and metastatic potential by regulating the Wnt/β-catenin signaling pathway.

scholarly journals Downregulation of SLC27A6 by DNA Hypermethylation Promotes Proliferation but Suppresses Metastasis of Nasopharyngeal Carcinoma Through Modulating Lipid Metabolism

2022 ◽  
Vol 11 ◽  
Author(s):  
Xuemin Zhong ◽  
Yanping Yang ◽  
Bo Li ◽  
Pan Liang ◽  
Yiying Huang ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Nasopharyngeal Carcinoma ◽  
Epithelial Mesenchymal Transition ◽  
Mrna Level ◽  
Promoter Hypermethylation ◽  
Migration And Invasion ◽  
Dna Hypermethylation ◽  
Mesenchymal Transition

Lipid is the building block and an important source of energy, contributing to the malignant behavior of tumor cells. Recent studies suggested that lipid droplets (LDs) accumulations were associated with nasopharyngeal carcinoma (NPC) progression. Solute carrier family 27 member 6 (SLC27A6) mediates the cellular uptake of long-chain fatty acid (LCFA), a necessary lipid component. However, the functions of SLC27A6 in NPC remain unknown. Here, we found a significant reduction of SLC27A6 mRNA in NPC tissues compared with normal nasopharyngeal epithelia (NNE). The promoter methylation ratio of SLC27A6 was greater in NPC than in non-cancerous tissues. The demethylation reagent 5-aza-2’-deoxycytidine (5-aza-dC) remarkably restored the mRNA expression of SLC27A6, suggesting that this gene was downregulated in NPC owing to DNA promoter hypermethylation. Furthermore, SLC27A6 overexpression level in NPC cell lines led to significant suppression of cell proliferation, clonogenicity in vitro, and tumorigenesis in vivo. Higher SLC27A6 expression, on the other hand, promoted NPC cell migration and invasion. In particular, re-expression of SLC27A6 faciliated epithelial-mesenchymal transition (EMT) signals in xenograft tumors. Furthermore, we observed that SLC27A6 enhanced the intracellular amount of triglyceride (TG) and total cholesterol (T-CHO) in NPC cells, contributing to lipid biosynthesis and increasing metastatic potential. Notably, the mRNA level of SLC27A6 was positively correlated with cancer stem cell (CSC) markers, CD24 and CD44. In summary, DNA promoter hypermethylation downregulated the expression of SLC27A6. Furthermore, re-expression of SLC27A6 inhibited the growth capacity of NPC cells but strengthened the CSC markers. Our findings revealed the dual role of SLC27A6 in NPC and shed novel light on the link between lipid metabolism and CSC maintenance.

SOX10 induces epithelial–mesenchymal transition and contributes to nasopharyngeal carcinoma progression

2018 ◽  
Vol 96 (3) ◽  
pp. 326-331 ◽  
Author(s):  
Ping He ◽  
Xiaojie Jin
Keyword(s):  
Cell Proliferation ◽  
Nasopharyngeal Carcinoma ◽  
Cell Lines ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Mesenchymal Transition

Objective: The aim of this study was to investigate the role of SOX10 in nasopharyngeal carcinoma (NPC) and the underlying molecular mechanisms. Methods: The expression of SOX10 was initially assessed in human NPC tissues and a series of NPC cell lines through quantitative real-time PCR (qRT-PCR) and Western blot. Then, cell proliferation, cycle, migration, and the invasiveness of NPC cells with knockdown of SOX10 were examined by MTT, flow cytometry, and Transwell migration and invasion assays, respectively. Finally, nude mice tumorigenicity experiments were performed to evaluate the effects of SOX10 on NPC growth and metastasis in vivo. Results: SOX10 was significantly increased in NPC tissues and cell lines. In-vitro experiments revealed that loss of SOX10 obviously inhibited cell proliferation, migration, and invasiveness, as well as the epithelial–mesenchymal transition (EMT) process in NPC cells. In-vivo experiments further demonstrated that disrupted SOX10 expression restrained NPC growth and metastasis, especially in lung and liver. Conclusion: Taken together, our data confirmed the role of SOX10 as an oncogene in NPC progression, and revealed that SOX10 may serve as a novel biomarker for diagnosis of NPC, as well as a potential therapeutic target against this disease.

scholarly journals PADI1 contributes to epithelial-mesenchymal transition in pancreatic ductal adenocarcinoma through activating ERK1/2-p38 signaling pathway

2021 ◽  
Author(s):  
Tengfei Ji ◽  
Keqiang Ma ◽  
Liang Chen ◽  
Tiansheng Cao
Keyword(s):  
Cell Migration ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Signaling Pathway ◽  
Epithelial Mesenchymal Transition ◽  
The Cancer Genome Atlas ◽  
Ductal Adenocarcinoma ◽  
Migration And Invasion ◽  
Survival Prognosis ◽  
Mesenchymal Transition

Abstract Background Peptidylarginine deiminase 1 (PADI1) may be relative with the progression of epithelial-mesenchymal transition (EMT) in pancreatic ductal adenocarcinoma (PAAD). We aim to explore the role of PADI1 in PAAD. Methods The expression pattern of PADI1 in PAAD tissues and normal tissues was analyzed using The Cancer Genome Atlas (TCGA) dataset. PADI1 was knocked down in CFPAN-1 and HPAC cells, while overexpressed in PANC-1 and Bxpc-3 cells by RNA interference. Wound healing assay was performed to analyze relative cell migration distance. Cell migration and invasion were assessed by Transwell assay. Related protein expression levels were measured by western blot and immunofluorescence. Results Bioinformatics analysis showed that PADI1 was overexpressed in PAAD tissues and associated with worse survival prognosis. Knockdown of PADI1 suppressed the cell migration, invasion and activated ERK1/2-p38 signaling pathway in CFPAN-1 and HPAC cells. Overexpression of PADI1 obtained the opposite results in PANC-1 and Bxpc-3 cells. Moreover, treatment with MEK1/2 inhibitor significantly recovered the effects of PADI1 knockdown on cell migration, invasion, EMT process and p-ERK1/2 and p38 expression in CFPAN-1 and HPAC cells. Conclusions Our data suggested that PADI1 may function as an oncogene in regulating metastasis in vitro in PAAD.

scholarly journals LncRNA ST7-AS1, by regulating miR-181b-5p/KPNA4 axis, promotes the malignancy of lung adenocarcinoma

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Rong-Hang Hu ◽  
Zi-Teng Zhang ◽  
Hai-Xiang Wei ◽  
Lu Ning ◽  
Jiang-Shan Ai ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Luciferase Assay ◽  
Migration And Invasion ◽  
Loss Of Function ◽  
Mesenchymal Transition

Abstract Background Growing evidence suggests that suppressor of tumorigenicity 7 antisense RNA 1 (ST7-AS1) is an oncogenic long noncoding RNA (lncRNA). However, little is known on its clinical significance, biological functions, or molecular mechanisms in lung adenocarcinoma (LUAD). Methods The expression of ST7-AS1 and miR-181b-5p were examined by qRT-PCR. The correlations between ST7-AS1 level and different clinicopathological features were analysed. In vitro, LUAD cells were examined for cell viability, migration and invasion by MTT, wound healing and Transwell assay, respectively. Epithelial-mesenchymal transition (EMT) biomarkers were detected by Western blot. The regulations between ST7-AS1, miR-181b-5p, and KPNA4 were examined by luciferase assay, RNA immunoprecipitation, RNA pulldown. Both gain- and loss-of-function strategies were used to assess the importance of different signalling molecules in malignant phenotypes of LUAD cells. The in vivo effect was analysed using the xenograft and the experimental metastasis mouse models. Results ST7-AS1 was upregulated in LUAD tissues or cell lines, correlated with tumours of positive lymph node metastasis or higher TNM stages, and associated with shorter overall survival of LUAD patients. ST7-AS1 essentially maintained the viability, migration, invasion, and EMT of LUAD cells. The oncogenic activities of ST7-AS1 were accomplished by sponging miR-181b-5p and releasing the suppression of the latter on KPNA4. In LUAD tissues, ST7-AS1 level positively correlated with that of KPNA4 and negatively with miR-181b-5p level. In vivo, targeting ST7-AS1 significantly inhibited xenograft growth and metastasis. Conclusions ST7-AS1, by regulating miR-181b-5p/KPNA4 axis, promotes the malignancy of LUAD cells. Targeting ST7-AS1 and KPNA4 or up-regulating miR-181b-5p, therefore, may benefit the treatment of LUAD.

scholarly journals miR-186 Suppresses the Progression of Cholangiocarcinoma Cells Through Inhibition of Twist1

2019 ◽  
Vol 27 (9) ◽  
pp. 1061-1068 ◽  
Author(s):  
Ming Zhang ◽  
Baochang Shi ◽  
Kai Zhang
Keyword(s):  
Cell Proliferation ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Tumor Formation ◽  
In Vitro Assays ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Cycle Arrest

Deregulation of miR-186 and Twist1 has been identified to be involved in the progression of multiple cancers. However, the detailed molecular mechanisms underlying miR-186-involved cholangiocarcinoma (CCA) are still unknown. In this study, we found that miR-186 was downregulated in CCA tissues and cell lines, and negatively correlated with the expression of Twist1 protein. In vitro assays demonstrated that miR-186 mimics repressed cell proliferation, in vivo tumor formation, and caused cell cycle arrest. miR-186 mimics also inhibited the migration and invasion of CCLP1 and SG-231 cells. Mechanistically, the 3′-untranslated region (3′-UTR) of Twist1 mRNA is a direct target of miR-186. Further, miR-186 inhibited the expressions of Twist1, N-cadherin, vimentin, and matrix metallopeptidase 9 (MMP9) proteins, whereas it increased the expression of E-cadherin in CCLP1 and SG-231 cells. Silencing of Twist1 expression enhanced the inhibitory effects of miR-186 on the proliferation, migration, and invasion of CCLP1 and SG-231 cells. In conclusion, miR-186 inhibited cell proliferation, migration, invasion, and epithelial‐mesenchymal transition (EMT) through targeting Twist1 in human CCA. Thus, miR-186/Twist1 axis may benefit the development of therapies for CCA.

scholarly journals METTL7B promotes migration and invasion in thyroid cancer through epithelial-mesenchymal transition

2019 ◽  
Vol 63 (1) ◽  
pp. 51-61 ◽  
Author(s):  
Danrong Ye ◽  
Yang Jiang ◽  
Yihan Sun ◽  
Yuefeng Li ◽  
Yefeng Cai ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Carcinoma ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Differentially Expressed Gene ◽  
Migration And Invasion ◽  
Endocrine Tumors ◽  
Mesenchymal Transition ◽  
Potential Biomarker

Thyroid cancer is associated with one of the most malignant endocrine tumors. However, molecular mechanisms underlying thyroid tumorigenesis and progression remain unclear. In order to investigate these mechanisms, we performed whole-transcriptome sequencing, which indicated that a differentially expressed gene, METTL7B, was highly expressed in thyroid cancers. We analyzed METTL7B expression using TCGA and performed qRT-PCR on tissue samples. Moreover, an analysis of clinicopathological characteristics revealed a positive correlation between METTL7B and lymph node metastasis. A series of in vitro experiments indicated that METTL7B enhanced migration and invasion of thyroid carcinoma cells. Further studies revealed that METTL7B may enhance TGF-β1-induced epithelial-mesenchymal transition (EMT). Our results indicate that METTL7B may promote metastasis of thyroid cancer through EMT and may therefore be considered as a potential biomarker for the diagnosis and prognosis of thyroid carcinoma.

scholarly journals ZNF224 is a Mediator of TGF-β Pro-oncogenic Function in Melanoma

2021 ◽  
Author(s):  
Elena Cesaro ◽  
Arianna Pastore ◽  
Alessia Polverino ◽  
Lorenzo Manna ◽  
Giuseppina Divisato ◽  
...  
Keyword(s):  
Transcriptional Activation ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Zinc Finger Protein ◽  
Epithelial Mesenchymal Transition ◽  
Metastatic Potential ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Regulatory Loop ◽  
Oncogenic Function

Abstract Background: The zinc finger protein ZNF224 plays a dual role in human cancers, operating as both tumour suppressor and oncogenic factor depending on the cellular context and molecular partners. In this research, we investigated the role played by ZNF224 in the TGF-β signalling in malignant melanoma. Methods: Real-time qPCR, western blot, and chromatin immunoprecipitation assays were performed to examine the molecular mechanisms of ZNF224 in TGF-β signalling in melanoma. ZNF224-induced cell anchorage, independent growth, migration, and invasion were assessed by the colony formation, wound healing, and transwell assays.Results: Our findings showed that ZNF224, whose expression increased in melanoma cell lines after TGF-b stimulation, potentiated the activation induced by TGF-β on its target genes involved in epithelial-mesenchymal transition (EMT). Accordingly, overexpression of ZNF224 improved the tumourigenic properties of melanoma cells, promoting cell proliferation and invasiveness, while ZNF224 knockdown had the opposite effect. Moreover, ZNF224 promoted the transcriptional activation of TGF-β itself and its type 1 and 2 receptors (TβR1 and TβR2), thus highlighting a possible mechanism by which ZNF224 could enhance the endogenous TGFβ/Smad signalling. Conclusions: Our results provide evidence for the involvement of ZNF224 in TGF-β signalling as a mediator of TGF-β pro-oncogenic function and unveil a positive regulatory loop between TGF-β and ZNF224 to promote EMT, consequently increasing the tumour metastatic potential.

scholarly journals Activation of Vimentin Is Critical to Promote a Metastatic Potential of Cholangiocarcinoma Cells

2018 ◽  
Vol 26 (4) ◽  
pp. 605-616 ◽  
Author(s):  
Waraporn Saentaweesuk ◽  
Norie Araki ◽  
Kulthida Vaeteewoottacharn ◽  
Atit Silsirivanit ◽  
Wunchana Seubwai ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Metastatic Cancer ◽  
Metastatic Tumor ◽  
Migration And Invasion ◽  
Vimentin Expression ◽  
Mesenchymal Transition ◽  
Tail Vein

Cholangiocarcinoma (CCA) is a highly metastatic tumor, and the majority of patients with CCA have a short survival time because there are no available effective treatments. Hence, a better understanding regarding CCA metastasis may provide an opportunity to improve the strategies for treatment. A comparison study between the highly metastatic cells and their parental cells is an approach to uncover the molecular mechanisms underlying the metastatic process. In the present study, a lung metastatic CCA cell line, KKU-214L5, was established by the in vivo selection of the tail vein-injected mouse model. KKU-214L5 cells possessed mesenchymal spindle-like morphology with higher migration and invasion abilities in vitro than the parental cells (KKU-214). KKU-214L5 also exhibited extremely aggressive lung colonization in the tail vein-injected metastatic model. Epithelial‐mesenchymal transition (EMT) was clearly observed in KKU-214L5 cells. Significant downregulation of epithelial markers (ZO-1 and claudin-1), with unique upregulation of E-cadherin and mesenchymal markers (vimentin, β-catenin, and slug), was observed in KKU-214L5. Increasing MMP-2 and MMP-9 activities and CD147 expression reflected the high invasion activity in KKU-214L5 cells. Suppression of vimentin using siRNA significantly decreased the migration and invasion capabilities of KKU-214L5 to almost the basal levels of the parental cells without any change on the expression levels of other EMT markers and the activities of MMPs. These results suggest that vimentin activation is essential to potentiate the metastatic characters of CCA cells, and suppression of vimentin expression could be a potential strategy to improve the treatment of CCA, a highly metastatic cancer.

scholarly journals XJP Inhibits Apoptosis, Invasion, EMT, and Wnt/Β-Catenin Pathway in Triple-Negative Breast Cancer

2021 ◽  
Author(s):  
Dandan Feng ◽  
Hongzhi Chen ◽  
Guangxi Shi ◽  
Mengdi Zhang ◽  
Hongyi Liang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Flow Cytometry ◽  
Triple Negative Breast Cancer ◽  
Molecular Mechanisms ◽  
Triple Negative ◽  
Epithelial Mesenchymal Transition ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Mesenchymal Transition

Abstract Background: Triple-negative breast cancer (TNBC) progresses at a rapid pace. Chemotherapy is a major clinical application. However, resistance and metastases are key barriers to chemotherapy. Xiaojin pills (XJP) have been used clinically for treating TNBC for decades. However, the potential molecular mechanisms of the effect of XJP on breast cancer is still not understood.Methods: The cell viability was analyzed using Cell Counting Kit-8 (CCK-8). Flow cytometry was used to detect apoptosis, and the migration and invasion abilities of TNBC were assessed using Transwell assay. For molecular mechanisms, the protein expression levels were determined by Western blot analysis. The expression of β-catenin in the Wnt/β-serial protein (β-catenin) pathway was detected with immunofluorescence (IF).Results: XJP inhibited the viability and proliferation of the TNBC cell line in vitro. Flow cytometry analysis showed that apoptosis increased in both MDA-MB-231 and MDA-MB-468 cells induced by XJP. The expression of the proteins associated with invasion, for example, matrix metalloproteinase (MMP) and MMP9, was reduced. Among epithelial–mesenchymal transition markers, E-cadherin was upregulated and N-cadherin was downregulated. The apoptosis-related proteins caspase-8, caspase-3, caspase-9, and Parp were all upregulated. Additionally, XJP effectively suppressed the expression of β-catenin, which belonged to the Wnt/β-catenin pathway.Conclusions: These results suggested that XJP suppressed the progression of TNBC cells by suppressing apoptosis, invasion, EMT, and Wnt/β-catenin pathway.

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