scholarly journals Mechanisms of JAK‑STAT signaling pathway mediated by CXCL8 gene silencing on epithelial‑mesenchymal transition of human cutaneous melanoma cells

2020 ◽  
Vol 20 (2) ◽  
pp. 1973-1981
Author(s):  
Xiaorui Hu ◽  
Lili Yuan ◽  
Teng Ma
Keyword(s):  
Gene Silencing ◽  
Signaling Pathway ◽  
Cutaneous Melanoma ◽  
Epithelial Mesenchymal Transition ◽  
Melanoma Cells ◽  
Mesenchymal Transition ◽  
Stat Signaling

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 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 HOXC10 promotes growth and migration of melanoma by regulating Slug to activate the YAP/TAZ signaling pathway

2021 ◽  
Author(s):  
Yuanxin Miao ◽  
Weina Zhang ◽  
Su Liu ◽  
Xiangfeng Leng ◽  
Chunnan Hu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Epithelial Mesenchymal Transition ◽  
Therapeutic Potential ◽  
Melanoma Cells ◽  
Mesenchymal Transition ◽  
Normal Tissues ◽  
Slug Expression ◽  
Melanoma Patients ◽  
And Migration

Abstract Homeobox C10 (HOXC10) has been reported to participate in various cancers. However, the involvement of HOXC10 in melanoma is still remains unknown. Here, we attempted to determine whether HOXC10 can affect the development of melanoma. We separated melanoma tissues and the matched tumor-adjacent normal tissues from melanoma patients, and examined HOXC10 expression in the melanoma cells and tissues. Comparing with the tumor-adjacent normal tissues, HOXC10 was up-regulated in melanoma tissues. Melanoma cells also displayed an up-regulation of HOXC10. Moreover, HOXC10 overexpression promoted cell proliferation, clone formation and inhibited apoptosis of melanoma cells. HOXC10 up-regulation also enhanced migration, invasion and epithelial-mesenchymal transition (EMT) in melanoma cells. Additionally, HOXC10 accelerated Slug expression by interacting with Slug, and activating the promoter of Slug. Slug activated the YAP/TAZ signaling pathway, which was reversed by HOXC10 silencing. The in vitro assays demonstrated that inhibition of HOXC10 significantly repressed tumor growth and lung metastasis of melanoma in mice by inhibiting Slug and YAP/TAZ signaling pathway. In conclusion, this work demonstrated that HOXC10 promoted growth and migration of melanoma by regulating Slug to activate the YAP/TAZ signaling pathway. Therefore, this study suggests that inhibition of HOXC10 has therapeutic potential in melanoma.

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.

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