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• W2290940734 abstract "In primary melanoma, the amount of vascular endothelial growth factor C (VEGF-C) expression and lymphangiogenesis predicts the probability of metastasis to sentinel nodes, but conditions boosting VEGF-C expression in melanoma are poorly characterized. By comparative mRNA expression analysis of a set of 22 human melanoma cell lines, we found a striking negative correlation between VEGF-C and microphthalmia-associated transcription factor (MITF) expression, which was confirmed by data mining in GEO databases of human melanoma Affymetrix arrays. Moreover, in human patients, high VEGF-C and low MITF levels in primary melanoma significantly correlated with the chance of metastasis. Pathway analysis disclosed the respective c-Jun N-terminal kinase and p38/mitogen-activated protein kinase activities as being responsible for the inverse regulation of VEGF-C and MITF. Predominant c-Jun N-terminal kinase signaling results in a VEGF-Clow/MITFhigh phenotype; these melanoma cells are highly proliferative, show low mobility, and are poorly lymphangiogenic. Predominant p38 signaling results in a VEGF-Chigh/MITFlow phenotype, corresponding to a slowly cycling, highly mobile, lymphangiogenic, and metastatic melanoma. In conclusion, the relative c-Jun N-terminal kinase and p38 activities determine the biological behavior of melanoma. VEGF-C and MITF levels serve as surrogate markers for the respective c-Jun N-terminal kinase and p38 activities and may be used to predict the risk of metastasis in primary melanoma. In primary melanoma, the amount of vascular endothelial growth factor C (VEGF-C) expression and lymphangiogenesis predicts the probability of metastasis to sentinel nodes, but conditions boosting VEGF-C expression in melanoma are poorly characterized. By comparative mRNA expression analysis of a set of 22 human melanoma cell lines, we found a striking negative correlation between VEGF-C and microphthalmia-associated transcription factor (MITF) expression, which was confirmed by data mining in GEO databases of human melanoma Affymetrix arrays. Moreover, in human patients, high VEGF-C and low MITF levels in primary melanoma significantly correlated with the chance of metastasis. Pathway analysis disclosed the respective c-Jun N-terminal kinase and p38/mitogen-activated protein kinase activities as being responsible for the inverse regulation of VEGF-C and MITF. Predominant c-Jun N-terminal kinase signaling results in a VEGF-Clow/MITFhigh phenotype; these melanoma cells are highly proliferative, show low mobility, and are poorly lymphangiogenic. Predominant p38 signaling results in a VEGF-Chigh/MITFlow phenotype, corresponding to a slowly cycling, highly mobile, lymphangiogenic, and metastatic melanoma. In conclusion, the relative c-Jun N-terminal kinase and p38 activities determine the biological behavior of melanoma. VEGF-C and MITF levels serve as surrogate markers for the respective c-Jun N-terminal kinase and p38 activities and may be used to predict the risk of metastasis in primary melanoma." @default.
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• W2290940734 date "2016-05-01" @default.
• W2290940734 modified "2023-10-18" @default.
• W2290940734 title "Opposing Roles of JNK and p38 in Lymphangiogenesis in Melanoma" @default.
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• W2290940734 doi "https://doi.org/10.1016/j.jid.2016.01.020" @default.
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