scholarly journals Cirsiliol Suppressed Epithelial to Mesenchymal Transition in B16F10 Malignant Melanoma Cells through Alteration of the PI3K/Akt/NF-κB Signaling Pathway

2019 ◽  
Vol 20 (3) ◽  
pp. 608 ◽  
Author(s):  
Priyanka Prasad ◽  
Andrea Vasas ◽  
Judit Hohmann ◽  
Anupam Bishayee ◽  
Dona Sinha
Keyword(s):  
Malignant Melanoma ◽  
Metastatic Melanoma ◽  
Signaling Pathway ◽  
Metastatic Disease ◽  
Molecular Mechanisms ◽  
Epithelial To Mesenchymal Transition ◽  
Epithelial Mesenchymal Transition ◽  
Nuclear Factor Κb ◽  
Melanoma Cells ◽  
Mesenchymal Transition

Malignant melanoma is a highly aggressive form of skin cancer which has a propensity for metastasis. Epithelial mesenchymal transition (EMT) plays a primordial role in the progression of metastatic disease. Metastatic melanoma is resistant to conventional therapies. Hence, researchers have been exploring alternative approaches, including the utility of bioactive phytochemicals to manage metastatic disease. In the present study, we investigated the potential of cirsiliol, a flavonoid isolated from Centaurea jacea L., in modulating the aggressive behavior of B16F10 metastatic melanoma cells, including EMT, and associated molecular mechanisms of action. Cirsiliol was found to be effective in restraining the colony formation and migration of fibronectin-induced B16F10 metastatic melanoma cells. Cirsiliol inhibited the activity and expression of matrix metalloproteinase-9 (MMP-9). Cirsiliol also suppressed the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (also known as Akt)/nuclear factor-κB (NF-κB) signaling pathway which, in turn, caused upregulation of E-cadherin and downregulation of N-cadherin, Snail and Twist. Based on these results, cirsiliol may be considered a promising compound against EMT in the therapeutic management of malignant melanoma.

scholarly journals WNT1 Inducible Signaling Pathway Protein 1 (WISP1) stimulates melanoma cell invasion and metastasis by promoting epithelial – mesenchymal transition

2018 ◽  
Author(s):  
Wentao Deng ◽  
Audry Fernandez ◽  
Sarah L. McLaughlin ◽  
David J. Klinke
Keyword(s):  
Signaling Pathway ◽  
Epithelial Mesenchymal Transition ◽  
Primary Melanoma ◽  
Gene Expression Signature ◽  
Melanoma Cells ◽  
Migration And Invasion ◽  
Matricellular Protein ◽  
Invasion And Metastasis ◽  
Mesenchymal Transition

ABSTRACTBesides intrinsic changes, malignant cells release soluble signals to reshape their microenvironment. Among the signaling factors is WNT1 inducible signaling pathway protein 1 (WISP1), a secreted matricellular protein that is elevated in a variety of cancers including melanoma and is associated with reduced overall survival of patients diagnosed with primary melanoma. In this work, we found thatWISP1knockout both increased cell proliferation and repressed wound healing, migration and invasion of mouse and human melanoma cells in an ensemble ofin vitroassays.In vivometastasis assays showed that WISP1 knockout repressed tumor metastasis in both C57BL/6Ncrl and NOD-scid IL2Rgammanull (NSG) mice with B16F10 and YUMM1.7 melanoma cells. Mechanistically, B16F10 cells that invaded in a transwell assay possessed a gene expression signature similar to Epithelial - Mesenchymal Transition (EMT), including coincident repression of E-cadherin and induction of fibronectin and N-cadherin. Upon WISP1 knockout, these EMT signature genes went in opposite directions in both mouse and human cell lines and were rescued by media containing WISP1 or recombinant WISP1 protein.In vivo,metastasis repression by WISP1 knockout was reversed by the reintroduction of either WISP1 or SNAI1. A set of EMT gene activation and inhibition experiments using recombinant WISP1 or kinase inhibitors in B16F10 and YUMM1.7 cells suggested that WISP1 activates Akt and MAP kinase signaling pathways to shift melanoma cells from a proliferative to invasive phenotype. Collectively, the results supported a model that WISP1 within the tumor microenvironment stimulates melanoma invasion and metastasis by promoting an EMT-like process.

scholarly journals MicroRNA-375: Potential cancer suppressor and therapeutic drug

2021 ◽  
Author(s):  
Jiahui Wei ◽  
Yiran Lu ◽  
Ruiqing Wang ◽  
Xiangzhu Xu ◽  
Qing Liu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Wnt Signaling Pathway ◽  
Human Tumor ◽  
Therapeutic Drug ◽  
Mesenchymal Transition

MiR-375 is a conserved noncoding RNA that is known to be involved in tumor cell proliferation, migration, and drug resistance. Previous studies have shown that miR-375 affects the epithelial-mesenchymal transition (EMT) of human tumor cells via some key transcription factors, such as Yes-associated protein 1 (YAP1), Specificity protein 1 (SP1) -and signaling pathways (Wnt signaling pathway, nuclear factor kappa B (NF-kB) pathway and transforming growth factor β (TGF-β) signaling pathway) and is vital for the development of cancer. Additionally, recent studies have identified miRNA delivery system carriers for improved in vivo transportation of miR-375 to specific sites. Here, we discussed the role of miR-375 in different types of cancers, as well as molecular mechanisms, and analyzed the potential of miR-375 as a molecular biomarker and therapeutic target to improve the efficiency of clinical diagnosis of cancer.

scholarly journals Effects of microRNA-136 on melanoma cell proliferation, apoptosis, and epithelial–mesenchymal transition by targetting PMEL through the Wnt signaling pathway

2017 ◽  
Vol 37 (5) ◽  
Author(s):  
Jiu-Jiang Wang ◽  
Zhi-Feng Li ◽  
Xiao-Jing Li ◽  
Zhao Han ◽  
Ling Zhang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Melanoma Cell ◽  
Epithelial Mesenchymal Transition ◽  
Wnt Signaling Pathway ◽  
Melanoma Cells ◽  
Model Group ◽  
Mesenchymal Transition ◽  
E Cadherin

The study aims to evaluate the effects of miR-136 on the proliferation, apoptosis, and epithelial–mesenchymal transition (EMT) of melanoma cells by targetting premelanosome protein (PMEL) through the Wnt signaling pathway. After establishment of melanoma mouse models, melanoma (model group) and normal tissues (normal group) were collected. Immunohistochemistry was performed to determine PMEL protein concentration. Mouse melanoma cells were assigned into control, blank, negative control (NC), miR-136 mimics, miR-136 inhibitors, siRNA-PMEL, and miR-136 inhibitors + siRNA-PMEL, LiC1 (Wnt signaling pathway activator), and siRNA-PMEL+ LiCl groups. MTT, Scratch test, Transwell assay, and flow cytometry were performed to measure cell proliferation, migration, invasion, and apoptosis. Quantitative real-time PCR (qRT-PCR) and Western blotting were performed to evaluate miR-136, PMEL, β-catenin, Wnt3a, Bcl-2, Bax, Caspase, E-cadherin, and N-cadherin expressions. PMEL is highly expressed in melanoma tissues. MiR-136, Bax, Caspase, and E-cadherin expressions decreased in the model group, whereas PMEL, β-catenin, Bcl-2, Wnt3a, and N-cadherin expressions increased. Bax, Caspase, and E-cadherin expressions increased in the miR-136 mimics and siRNA-PMEL groups, whereas the expressions decreased in the miR-136 inhibitors group and LiC1 group. PMEL, β-catenin, Bcl-2, Wnt3a, and N-cadherin expressions, cell proliferation, migration, and invasion decreased, and the apoptosis rate inceased in the miR-136 mimics and siRNA-PMEL groups; whereas the tendencies were opposite to those in the miR-136 inhibitors group and LiC1 group. In the siRNA-PMEL+ LiCl group, PMEL expression decreased. These findings indicated that overexpression of miR-136 inhibits melanoma cell EMT, proliferation, migration, invasion, and promotes apoptosis by targetting PMEL through down-regulation of the Wnt signaling pathway.

scholarly journals From Proteomic Mapping to Invasion-Metastasis-Cascade Systemic Biomarkering and Targeted Drugging of Mutant BRAF-Dependent Human Cutaneous Melanomagenesis

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2024
Author(s):  
Aikaterini F. Giannopoulou ◽  
Athanassios D. Velentzas ◽  
Athanasios K. Anagnostopoulos ◽  
Adamantia Agalou ◽  
Nikos C. Papandreou ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Epithelial To Mesenchymal Transition ◽  
Hypoxia Inducible Factor ◽  
Primary Melanoma ◽  
Melanoma Cells ◽  
Mesenchymal Transition ◽  
Mesenchymal To Epithelial Transition ◽  
Liquid Chromatography Tandem Mass ◽  
Novel Biomarkers

Melanoma is classified among the most notoriously aggressive human cancers. Despite the recent progress, due to its propensity for metastasis and resistance to therapy, novel biomarkers and oncogenic molecular drivers need to be promptly identified for metastatic melanoma. Hence, by employing nano liquid chromatography-tandem mass spectrometry deep proteomics technology, advanced bioinformatics algorithms, immunofluorescence, western blotting, wound healing protocols, molecular modeling programs, and MTT assays, we comparatively examined the respective proteomic contents of WM115 primary (n = 3955 proteins) and WM266-4 metastatic (n = 6681 proteins) melanoma cells. It proved that WM115 and WM266-4 cells have engaged hybrid epithelial-to-mesenchymal transition/mesenchymal-to-epithelial transition states, with TGF-β controlling their motility in vitro. They are characterized by different signatures of SOX-dependent neural crest-like stemness and distinct architectures of the cytoskeleton network. Multiple signaling pathways have already been activated from the primary melanoma stage, whereas HIF1α, the major hypoxia-inducible factor, can be exclusively observed in metastatic melanoma cells. Invasion-metastasis cascade-specific sub-routines of activated Caspase-3-triggered apoptosis and LC3B-II-dependent constitutive autophagy were also unveiled. Importantly, WM115 and WM266-4 cells exhibited diverse drug response profiles, with epirubicin holding considerable promise as a beneficial drug for metastatic melanoma clinical management. It is the proteome navigation that enables systemic biomarkering and targeted drugging to open new therapeutic windows for advanced disease.

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.

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