CLEC12B Decreases Melanoma Proliferation by Repressing Signal Transducer and Activator of Transcription 3.
J Invest Dermatol
; 142(2): 425-434, 2022 02.
Article
en En
| MEDLINE
| ID: mdl-34310951
ABSTRACT
The potential role of CLEC12B, a gene predominantly expressed by skin melanocytes discovered through transcriptomic analysis, in melanoma is unknown. In this study, we show that CLEC12B expression is lower in melanoma and melanoma metastases than in melanocytes and benign melanocytic lesions and that its decrease correlates with poor prognosis. We further show that CLEC12B recruits SHP2 phosphatase through its immunoreceptor tyrosine-based inhibition motif domain, inactivates signal transducer and activator of transcription 1/3/5, increases p53/p21/p27 expression/activity, and modulates melanoma cell proliferation. The growth of human melanoma cells overexpressing CLEC12B in nude mice after subcutaneous injection is significantly decreased compared with that in the vehicle control group and is associated with decreased signal transducer and activator of transcription 3 phosphorylation and increased p53 levels in the tumors. Reducing the level of CLEC12B had the opposite effect. We show that CLEC12B represses the activation of the signal transducer and activator of transcription pathway and negatively regulates the cell cycle, providing a proliferative asset to melanoma cells.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias Cutáneas
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Receptores Mitogénicos
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Lectinas Tipo C
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Factor de Transcripción STAT3
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Proteína Tirosina Fosfatasa no Receptora Tipo 11
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Melanoma
Tipo de estudio:
Observational_studies
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Prognostic_studies
Límite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
J Invest Dermatol
Año:
2022
Tipo del documento:
Article