Genetic and Genomic Pathways of Melanoma Development, Invasion and Metastasis

Motwani, Jyoti; Eccles, Michael R.

doi:10.3390/genes12101543

Cited by 19 publications

(11 citation statements)

References 161 publications

(206 reference statements)

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“…The biological functions of VEGF-A are exerted through its binding to two tyrosine kinase receptors, VEGFR1 and VEGFR2, expressed in vascular endothelial cells. VEGF-A plays an important role in tumor angiogenesis by enhancing the proliferation and motility of endothelial cells (Motwani and Eccles 2021). Several studies have shown that various cancer cells produce VEGF-A and express its receptors, VEGFR1 and/or VEGFR2 (von Marschall et al 2000;Carrillo de Santa Pau et al 2009;Hlobilkova et al 2009;Sopo et al 2019).…”

Section: Discussionmentioning

confidence: 99%

“… 1998 ; Guo et al . 2021 ; Motwani and Eccles 2021 ). VEGF is a potent angiogenic factor that binds to two tyrosine kinase-type receptors, VEGF receptor-1 (VEGFR1)/fms-like tyrosine kinase (Flt-1) and VEGFR2/kinase insert domain receptor (KDR)/fetal liver kinase 1, which are specifically and highly expressed in vascular endothelial cells.…”

Section: Introductionmentioning

confidence: 99%

“…Tumor cells are known to produce growth factors and cytokines, such as vascular endothelial growth factor (VEGF), transforming growth factors, and basic fibroblast growth factors, which have various biological activities in tumor cells and stroma cells, including endothelial cells and fibroblasts (Hayashido et al 1998;Guo et al 2021;Motwani and Eccles 2021). VEGF is a potent angiogenic factor that binds to two tyrosine kinase-type receptors, VEGF receptor-1 (VEGFR1)/fms-like tyrosine kinase (Flt-1) and VEGFR2/kinase insert domain receptor (KDR)/fetal liver kinase 1, which are specifically and highly expressed in Koichi Koizumi and Tomoaki Shintani contributed equally to this work.…”

Section: Introductionmentioning

confidence: 99%

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VEGF-A promotes the motility of human melanoma cells through the VEGFR1–PI3K/Akt signaling pathway

Koizumi

Shintani

Hayashido

et al. 2022

In Vitro Cell.Dev.Biol.-Animal

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Vascular endothelial growth factor A (VEGF-A) and its receptors (VEGFR1 and R2) play important roles in the progression of malignant melanoma through tumor angiogenesis. However, it is not clear whether the VEGF-A/VEGFR1 signaling pathway is involved in the proliferation and migration of melanoma cells. Thus, the effect of VEGF-A on cell migration was investigated in human melanoma cell lines. Of several splicing variants of VEGF-A, VEGF165 is the most abundant and responsible for VEGF-A biological potency. VEGF165 facilitated the migration of melanoma cells in both a chemotactic and chemokinetic manner, but cell proliferation was not affected by VEGF165. VEGF165 also induced the phosphorylation of Akt. In addition, VEGF165-induced cell migration was inhibited significantly by VEGFR1/2 or a VEGFR1-neutralizing antibody. Furthermore, the downregulation of VEGFR1 via the transfection of VEGFR1-targeting antisense oligonucleotides suppressed VEGF165-induced cell migration. Moreover, wortmannin, an inhibitor of phosphatidylinositol-3 kinase (PI3K) in the PI3K/Akt pathway, suppressed VEGF165-induced Akt phosphorylation and VEGF165-induced cell migration. These findings suggest that the motility of melanoma cells is regulated by signals mediated through the PI3K/Akt kinase pathway with the activation of VEGFR1 tyrosine kinase by VEGF165. Thus, the downregulation of signaling via VEGF-A/VEGFR1 might be an effective therapeutic approach that could prevent the progression of malignant melanoma.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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VEGF-A promotes the motility of human melanoma cells through the VEGFR1–PI3K/Akt signaling pathway

Koizumi

Shintani

Hayashido

et al. 2022

In Vitro Cell.Dev.Biol.-Animal

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“…The mechanism involved in tumor development and dissemination of cancer cells is still poorly understood and numerous proteins, miRNAs and signaling pathways have been reported to regulate this process [1,2]. Among these, endoglin, an auxiliary receptor of the transforming growth factor b (TGF-b) family, has emerged as a promising therapeutic target [3,4].…”

Section: Introductionmentioning

confidence: 99%

Correlation Between Endoglin and Malignant Phenotype in Human Melanoma Cells: Analysis of hsa-mir-214 and hsa-mir-370 in Cells and Their Extracellular Vesicles

Ruíz-Llorente

Ruiz-Rodríguez

Savini

et al. 2023

Advances in Experimental Medicine and Biology

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Endoglin (CD105) is an auxiliary receptor of transforming growth factor (TGF)-β family members that is expressed in human melanomas. It is heterogeneously expressed by primary and metastatic melanoma cells, and endoglin targeting as a therapeutic strategy for melanoma tumors is currently been explored. However, its involvement in tumor development and malignancy is not fully understood. Here, we find that endoglin expression correlates with malignancy of primary melanomas and cultured melanoma cell lines. Next, we have analyzed the effect of ectopic endoglin expression on two miRNAs (hsa-mir-214 and hsa-mir-370), both involved in melanoma tumor progression and endoglin regulation. We show that compared with control cells, overexpression of endoglin in the WM-164 melanoma cell line induces; (i) a significant increase of hsa-mir-214 levels in small extracellular vesicles (EVs) as well as an increased trend in cells; and (ii) significantly lower levels of hsa-mir-370 in the EVs fractions, whereas no significant differences were found in cells. As hsa-mir-214 and hsa-mir-370 are not just involved in melanoma tumor progression, but they can also target endoglin-expressing endothelial cells in the tumor vasculature, these results suggest a complex and differential regulatory mechanism involving the intracellular and extracellular signaling of hsa-mir-214 and hsa-mir-370 in melanoma development and progression.

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“…Increasing evidences showed that many genes involved the development and progression of melanoma, most recurrent mutation is BRAFV600E, which hyperactivates the mitogen-activated protein kinase (MAPK) pathway ( 3 ) followed by NRAS mutation ( 4 ) and NF1 mutations ( 5 ). Among the regulatory pathways implicated in melanoma, MAPK pathway is most common, others include PI3K pathway, Wingless type MMTV integration site (Wnt) signaling ( 6 ). Although the treatment of melanoma has been greatly improved in recent years, the prognosis of tumor patients remains poor due to individual differences.…”

Section: Introductionmentioning

confidence: 99%

A novel melanoma prognostic model based on the ferroptosis-related long non-coding RNA

et al. 2022

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Ferroptosis is an iron-dependent programmed cell death related to the biological process of many kinds of tumors. Long noncoding RNAs (LncRNA) have been found to play essential roles in the tumor, and their functions in the ferroptosis of tumor cells have been partially discovered. However, there is no summary of ferroptosis-related LncRNA and its functions in melanoma. In the present study, we aim to explore the expression profile of ferroptosis-related LncRNA genes and their value in melanoma prognosis by bioinformatics analysis. The expression of ferroptosis-related gene (FRG) from melanoma clinical data was extracted based on the Cancer Genome Atlas (TCGA) database. By screening the RNA expression data of 472 cases of melanoma and 810 cases of normal skin, eighteen ferroptosis-related differential genes were found to be related to the overall survival rate. Furthermore, 384 ferroptosis-related LncRNAs were discovered through constructing the mRNA-LncRNA co-expression network, and ten of them were found with prognostic significance in melanoma by multivariate Cox analysis. Risk assessment showed that the high expression of LncRNA00520 is associated with poor prognosis, while the increased expression of the other LncRNA is beneficial to the prognosis of patients with melanoma. From univariate and multivariate Cox regression analysis, there were ten ferroptosis-related LncRNA risk models towards to be significant independent prognostic factors for patients with melanoma and valuable predictive factors for overall survival (OS)(P<0.05). The ROC curve further suggested that the risk score has relatively reliable predictive ability (AUC=0.718). The protein level of ferroptosis-related genes was verified by the HPA database and IHC test, leading to the discovery that the expressions of ALOX5, PEBP1, ACSL4, and ZEB1 proteins up-regulated in tumor tissues, and existed differences between tumor tissues and normal tissues. In conclusion, we identified ten ferroptosis-related LncRNA and constructed a prognosis model base.

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Genetic and Genomic Pathways of Melanoma Development, Invasion and Metastasis

Cited by 19 publications

References 161 publications

VEGF-A promotes the motility of human melanoma cells through the VEGFR1–PI3K/Akt signaling pathway

VEGF-A promotes the motility of human melanoma cells through the VEGFR1–PI3K/Akt signaling pathway

Correlation Between Endoglin and Malignant Phenotype in Human Melanoma Cells: Analysis of hsa-mir-214 and hsa-mir-370 in Cells and Their Extracellular Vesicles

A novel melanoma prognostic model based on the ferroptosis-related long non-coding RNA

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