Roles of p38α and p38ß mitogenactivated protein kinase isoforms in human malignant melanoma A375 cells.
Int J Mol Med
; 44(6): 2123-2132, 2019 Dec.
Article
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| MEDLINE
| ID: mdl-31661126
ABSTRACT
Skin cancer is one of the most common cancers worldwide. Melanoma accounts for ~5% of skin cancers but causes the large majority of skin cancerrelated deaths. Recent discoveries have shown that the mitogenactivated protein kinase (MAPK) signaling pathway is critical for melanoma development and progression. Many oncogenic pathways that cause melanoma tumorigenesis have been identified, most of which are due to RAF/MEK/ERK (MAPK) pathway activation. However, the precise role of p38 remains unclear. Using specific short hairpin (sh) RNA to silence p38α and p38ß, the present findings demonstrated that p38α was a crucial factor in regulating cell migration in the A375 melanoma cell line. Silencing p38α downregulated the expression of epithelialmesenchymal transition markers, such as matrix metallopeptidase (MMP) 2, MMP9, twist family bHLH transcription factor 1, snail family transcriptional repressor 1 and vimentin, while mesenchymalepithelial transition markers, such as Ecadherin, were upregulated. Of note, the results also demonstrated that p38α silencing impaired vascular endothelial growth factor expression, which regulates tumor angiogenesis. Furthermore, p38α knockdown inhibited cell proliferation in melanoma cells. In addition, silencing p38α induced senescencelike features, but not cell cycle arrest. Expression of the senescence markers p16, p21, p53 and ßgalactosidase was upregulated, and an increase in the number of senescenceassociated ßgalactosidasepositive cells was observed in a p38α knockdown stable clone. However, no significant difference was found between control and p38ß stable knockdown cells. Taken together, the present results suggested that p38α knockdown impaired migration and proliferation, and increased senescence, in A375 melanoma cells. However, p38ß may not be involved in melanoma tumorigenesis. Therefore, targeting p38α may be a valuable approach towards inhibiting tumor growth and metastasis in patients with melanoma.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Proteína Quinasa 11 Activada por Mitógenos
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Proteína Quinasa 14 Activada por Mitógenos
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Proliferación Celular
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Melanoma
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Int J Mol Med
Asunto de la revista:
BIOLOGIA MOLECULAR
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GENETICA MEDICA
Año:
2019
Tipo del documento:
Article