Dual, enzymatic and non-enzymatic, function of ecto-5'-nucleotidase (eN, CD73) in migration and invasion of A375 melanoma cells.

Ecto-5'-nucleotidase (eN, CD73) mediates extracellular adenosine production from 5'-AMP. Non-enzymatic functions of eN have also been reported. The aim of the study was to investigate the role of ecto-5'-nucleotidase in aggressive melanoma behaviour. Analysis of the involvement of eN in adhesion, migration and invasion revealed eN functions unknown to date. We found that following eN blockade by concanavalin A, the strength of adhesion to different ECM proteins was not altered, but at the same time the invasion ability of the cells was decreased. On the other hand, knocking down eN in melanoma cells did not influence cell invasion but abolished their migration on tenascin C (TnC). Ecto-5'-nucleotidase seems to fulfil a more distinct role as a receptor than as an enzyme in the cell interaction and mobility on TnC. Ecto-5'-nucleotidase activates also focal adhesion kinase and enhances the formation of complexes upon cell adhesion to TnC. All these observations prove that an eN-TnC complex is involved in cell migration and invasion and thus in the regulation of melanoma progression.

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Bornyl cis-4-Hydroxycinnamate Suppresses Cell Metastasis of Melanoma through FAK/PI3K/Akt/mTOR and MAPK Signaling Pathways and Inhibition of the Epithelial-to-Mesenchymal Transition

International Journal of Molecular Sciences ◽

10.3390/ijms19082152 ◽

2018 ◽

Vol 19 (8) ◽

pp. 2152 ◽

Cited By ~ 8

Author(s):

Tzu-Yen Yang ◽

Mei-Li Wu ◽

Chi-I Chang ◽

Chih-I Liu ◽

Te-Chih Cheng ◽

...

Keyword(s):

Cell Migration ◽

Signaling Pathways ◽

Melanoma Cell ◽

Epithelial To Mesenchymal Transition ◽

Melanoma Cells ◽

Migration And Invasion ◽

Mesenchymal Transition ◽

Cell Migration And Invasion ◽

Cell Metastasis ◽

A375 Melanoma

Bornyl cis-4-hydroxycinnamate, a bioactive compound isolated from Piper betle stems, has the potential for use as an anti-cancer agent. This study investigated the effects of bornyl cis-4-hydroxycinnamate on cell migration and invasion in melanoma cells. Cell migration and invasion were compared in A2058 and A375 melanoma cell lines treated with/without bornyl cis-4-hydroxycinnamate (1–6 µM). To examine whether bornyl cis-4-hydroxycinnamate has a potential anti-metastatic effect on melanoma cells, cell migration and invasion assays were performed using a Boyden chamber assay and a transwell chamber in A2058 and A375 cells. Gelatin zymography was employed to determine the enzyme activities of MMP-2 and MMP-9. Cell lysates were collected for Western blotting analysis of matrix metalloproteinase (MMP)-2, MMP-9 and tissue inhibitors of metalloproteinase-1/2 (TIMP-1/2), as well as key molecules in the mitogen-activated protein kinase (MAPK), focal adhesion kinase (FAK)/ phosphatidylinositide-3 kinases (PI3K)/Akt/ mammalian target of rapamycin (mTOR), growth factor receptor-bound protein 2 (GRB2) signaling pathways. Our results demonstrated that bornyl cis-4-hydroxycinnamate is a potentially useful agent that inhibits melanoma cell migration and invasion, and altered melanoma cell metastasis by reducing MMP-2 and MMP-9 expression through inhibition of the FAK/PI3K/Akt/mTOR, MAPK, and GRB2 signaling pathways. Moreover, bornyl cis-4-hydroxycinnamate inhibited the process of the epithelial-to-mesenchymal transition in A2058 and A375 melanoma cells. These findings suggested that bornyl cis-4-hydroxycinnamate has potential as a chemotherapeutic agent, and warrants further investigation for its use in the management of human melanoma.

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Pharmacological Inhibition of USP7 Supresses Growth and Metastasis of Melanoma Cells in Vitro and in Vivo

10.21203/rs.3.rs-117715/v1 ◽

2020 ◽

Author(s):

Minmin Xiang ◽

Long Liang ◽

Xinwei Kuang ◽

Zuozhong Xie ◽

Jing Liu ◽

...

Keyword(s):

Scratch Test ◽

Resistance Mechanisms ◽

Melanoma Cells ◽

Migration And Invasion ◽

Western Blot Assay ◽

Novel Therapeutic Strategies ◽

Novel Therapeutic

Abstract Background: Melanoma is a highly aggressive type of skin cancer. Due to the development of diverse resistance mechanisms and severe adverse side effects, significantly limits the efficiency of current therapeutic approaches. Identification of the new therapeutic targets involved in the pathogenesis will benefit to develop novel therapeutic strategies. The deubiquitinase USP7(ubiquitin-specific protease-7) is deregulated in serval cancer types, as a potential target for cancer treatment, but its role in melanoma is still unclear. Here, we investigated the role of USP7 and its inhibitor P22077 in melanoma treatment.Methods: To explore the role of USP7 and the anti-tuomr effect of P22077 in melanma progression and metastasis, a series of cell biological, molecular and biochemical approaches were used for in vitro and in vivo investigations.These methods included RT-qPCR, Western blot assay, cell transfection, CCK8 assay, flow cytometry, scratch test, Transwell assay, mouse xenograft,TUNEL staining.Results:The USP7 inhibitor P22077 suppressed the growth of melanoma in vitro and in vivo. additionally, P22077 induction of cell cycle arrest and apoptosis via ROS(reactive oxygen species) accumulation-induced DNA damage. Furthermore, inhibition of USP7 also prevented migration and invasion of melanoma cells in vitro and in vivo by decrease the Wnt/β-catenin signal pathway. Conclusion: Our data indicated that USP7 acts as an oncogene involved in melanoma cell proliferation and metastasis and may provide a novel therapeutic target for melanoma treatment.

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Olig2 regulates p53-mediated apoptosis, migration and invasion of melanoma cells

Scientific Reports ◽

10.1038/s41598-021-87438-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Ji Eun Lee ◽

Sungjin Ahn ◽

Haengdueng Jeong ◽

Seungchan An ◽

Cheol Hwan Myung ◽

...

Keyword(s):

Transcription Factor ◽

Enzyme Activity ◽

Malignant Cell ◽

Melanoma Cells ◽

Migration And Invasion ◽

High Recurrence Rate ◽

Metastatic Progression ◽

Helix Loop Helix ◽

The Central Nervous System

AbstractMelanoma is a disease with a high recurrence rate and poor prognosis; therefore, the need for targeted therapeutics is steadily increasing. Oligodendrocyte transcription factor2 (Olig2) is a basic helix-loop-helix transcription factor that is expressed in the central nervous system during embryonic development. Olig2 is overexpressed in various malignant cell lines such as lung carcinoma, glioma and melanoma. Olig2 is known as a key transcription factor that promotes tumor growth in malignant glioma. However, the role of Olig2 in melanoma is not well characterized. We analyzed the role of Olig2 in apoptosis, migration, and invasion of melanoma cells. We confirmed that Olig2 was overexpressed in melanoma cells and tissues. Reduction of Olig2 increased apoptosis in melanoma cells by increasing p53 level and caspase-3/-7 enzyme activity. In addition, downregulation of Olig2 suppressed migration and invasion of melanoma cells by inhibiting EMT. Reduction of Olig2 inhibited expression of MMP-1 and the enzyme activity of MMP-2/-9 induced by TGF-β. Moreover, Olig2 was involved in the downstream stages of MEK/ERK and PI3K/AKT, which are major signaling pathways in metastatic progression of melanoma. In conclusion, this study demonstrated the crucial roles of Olig2 in apoptosis, migration, and invasion of melanoma and may help to further our understanding of the relationship between Olig2 and melanoma progression.

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Abstract 481: The role of jaspamide in the actin cytoskeleton of melanoma cells: The relation between migration and invasion

10.1158/1538-7445.am2012-481 ◽

2012 ◽

Author(s):

Michelle S. Menezes ◽

Adam Martens ◽

Evandro Luis O. Niero ◽

Fabio Siviero ◽

Glaucia M. Machado-Santelli

Keyword(s):

Actin Cytoskeleton ◽

Melanoma Cells ◽

Migration And Invasion

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BEL β-Trefoil Reduces the Migration Ability of RUNX2 Expressing Melanoma Cells in Xenotransplanted Zebrafish

Molecules ◽

10.3390/molecules25061270 ◽

2020 ◽

Vol 25 (6) ◽

pp. 1270 ◽

Cited By ~ 1

Author(s):

Maria Teresa Valenti ◽

Giulia Marchetto ◽

Massimiliano Perduca ◽

Natascia Tiso ◽

Monica Mottes ◽

...

Keyword(s):

Melanoma Cells ◽

Migration And Invasion ◽

In Vivo Model ◽

Wild Mushroom ◽

Migration Ability ◽

Melanoma Patients ◽

Annual Mortality

RUNX2, a master osteogenic transcript ion factor, is overexpressed in several cancer cells; in melanoma it promotes cells migration and invasion as well as neoangiogenesis. The annual mortality rates related to metastatic melanoma are high and novel agents are needed to improve melanoma patients’ survival. It has been shown that lectins specifically target malignant cells since they present the Thomsen–Friedenreich antigen. This disaccharide is hidden in normal cells, while it allows selective lectins binding in transformed cells. Recently, an edible lectin named BEL β-trefoil has been obtained from the wild mushroom Boletus edulis. Our previous study showed BEL β-trefoil effects on transcription factor RUNX2 downregulation as well as on the migration ability in melanoma cells treated in vitro. Therefore, to better understand the role of this lectin, we investigated the BEL β-trefoil effects in a zebrafish in vivo model, transplanted with human melanoma cells expressing RUNX2. Our data showed that BEL β-trefoil is able to spread in the tissues and to reduce the formation of metastases in melanoma xenotransplanted zebrafish. In conclusion, BEL β-trefoil can be considered an effective biomolecule to counteract melanoma disease.

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463 Autocrine regulation of receptor for advanced glycation endproducts (RAGE) by S100A4 promotes migration and invasion in A375 melanoma cells

European Journal of Cancer Supplements ◽

10.1016/s1359-6349(10)71264-7 ◽

2010 ◽

Vol 8 (5) ◽

pp. 118-119

Author(s):

S.C. Wolf ◽

C. Haase-Kohn ◽

J. Lenk ◽

J. Pietzsch

Keyword(s):

Advanced Glycation Endproducts ◽

Melanoma Cells ◽

Migration And Invasion ◽

Advanced Glycation ◽

Glycation Endproducts ◽

Autocrine Regulation ◽

A375 Melanoma

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Regulatory role of tetraspanin CD9 in tumor–endothelial cell interaction during transendothelial invasion of melanoma cells

Blood ◽

10.1182/blood.v98.13.3717 ◽

2001 ◽

Vol 98 (13) ◽

pp. 3717-3726 ◽

Cited By ~ 80

Author(s):

Natividad Longo ◽

Marı́a Yáñez-Mó ◽

Marı́a Mittelbrunn ◽

Gonzalo de la Rosa ◽

Marı́a-Luisa Muñoz ◽

...

Keyword(s):

Contact Area ◽

Critical Role ◽

Time Lapse ◽

Cell Interaction ◽

Inhibitory Effect ◽

Melanoma Cells ◽

Collagen Matrices ◽

3 Dimensional ◽

Heterotypic Interactions

Abstract Heterotypic interaction among tumor cells (TCs) and endothelial cells (ECs) may play a critical role during the vascular dissemination of neoplastic cells and during pathologic angiogenesis in tumors. To identify molecules involved in these processes, the distribution of vascular junctional proteins was first studied by immunofluorescence at sites of heterologous intercellular contact using TC-EC mosaic monolayers grown on 2-dimensional collagen. Several members of the tetraspanin superfamily, including CD9, CD81, and CD151, were found to localize at the TC-EC contact area. The localization of tetraspanins to the TC-EC heterologous contact area was also observed during the active transmigration of TCs across EC monolayers grown onto 3-dimensional collagen matrices. Dynamic studies by time-lapse immunofluorescence confocal microscopy showed an active redistribution of endothelial CD9 to points of melanoma insertion. Anti-CD9 monoclonal antibodies were found to specifically inhibit the transendothelial migration of melanoma cells; the inhibitory effect was likely caused by a strengthening of CD9-mediated heterotypic interactions of TCs to the EC monolayer. These data support a novel mechanism of tetraspanin-mediated regulation of TC transcellular migration independent of TC motility and growth during metastasis and a role for these molecules in the formation of TC-EC mosaic monolayers during tumor angiogenesis.

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IRF4-activated TEX41 promotes the malignant behaviors of melanoma cells by targeting miR-103a-3p/C1QB axis

BMC Cancer ◽

10.1186/s12885-021-09039-1 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Yingna Zheng ◽

Wu Zhou ◽

Min Li ◽

Ruixue Xu ◽

Shuai Zhang ◽

...

Keyword(s):

Melanoma Cell ◽

Melanoma Cells ◽

Migration And Invasion ◽

Transcriptional Level ◽

Potential Therapeutic Target ◽

Expression Of Genes ◽

Melanoma Cell Proliferation ◽

Non Coding Rnas ◽

The Relationship

Abstract Background Malignant melanoma is an aggressive skin cancer and a tumor of melanocytic origin. Recent studies have suggested that long non-coding RNAs (lncRNAs) play crucial regulatory roles in multiple malignancies, including melanoma. Testis expressed 41 (TEX41) is a relatively new lncRNA whose mechanism in melanoma remains vague. Aims This study aimed to explore the role and specific mechanism of TEX41 in melanoma. Methods The expression of genes involved in this study was determined by qRT-PCR. Functional assays were conducted to analyze the role of relevant genes in melanoma cells. The interaction between TEX41 promoter and IRF4 as well as the relationship among TEX41, miR-103a-3p and C1QB was verified by mechanism assays. Results IRF4 up-regulated TEX41 at the transcriptional level in melanoma cells. TEX41 knockdown hindered melanoma cell proliferation, migration and invasion while promoting cell apoptosis. TEX41 bound to miR-103a-3p and regulated C1QB. The suppressive impact of TEX41 depletion on melanoma cell malignant behaviors could be counteracted by miR-103a-3p inhibition or C1QB overexpression. Moreover, IRF4 could facilitate melanoma cell growth via up-regulating C1QB. Conclusions IRF4-activated TEX41 sequestered miR-103a-3p and modulated C1QB to promote melanoma cell malignant behaviors, for which TEX41 might be regarded as a potential therapeutic target for melanoma.

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