YAP activation in melanoma contributes to anoikis resistance and metastasis.
Exp Biol Med (Maywood)
; 246(8): 888-896, 2021 04.
Article
em En
| MEDLINE
| ID: mdl-33307801
ABSTRACT
Melanoma is inherently heterogeneous, providing resistance to apoptosis. Anoikis resistance is a hallmark feature of metastatic melanoma to escape apoptosis when cells lose contact with adjacent cells or extracellular matrix. The yes-associated protein transcription co-activator is the effector of Hippo pathway. Herein, we investigated the function of yes-associated protein in anoikis resistance of melanoma cells. When melanoma cells were grown under anchorage-independent condition, anoikis-resistant cells displayed higher levels of yes-associated protein activation than the cells that were attached to the basement membrane, as evidenced by downregulated phosphorylated yes-associated protein at Ser127 and higher expression of downstream genes BCL2 and MCL-1. Yes-associated protein overexpression directly enhanced the anoikis resistance and metastatic potential of melanoma cells. Conversely, yes-associated protein inhibitor CA3 exhibited Dose-dependent induction of anoikis in resistant melanoma cells and exerted great inhibition on cell migration. Knockdown of yes-associated protein expression by shRNA also rendered melanoma cells susceptible to anoikis and interrupted cell invasiveness. Yes-associated protein inhibition in anoikis-resistant cells also reduced the number of metastatic nodules in the lung sections of SCID mice. Clinically, higher yes-associated protein level in the lung metastasis tissues correlated with higher BCL2 and MCL1 expressions compared with the non-metastasis tissues. Overall, our finding suggests that the aberrant activation of yes-associated protein exerts important role on anoikis resistance and metastatic capability of melanoma cells.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
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Proteínas Proto-Oncogênicas c-bcl-2
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Anoikis
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Proteínas Adaptadoras de Transdução de Sinal
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Proteína de Sequência 1 de Leucemia de Células Mieloides
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Neoplasias Pulmonares
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Melanoma
Limite:
Animals
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Humans
Idioma:
En
Revista:
Exp Biol Med (Maywood)
Assunto da revista:
BIOLOGIA
/
FISIOLOGIA
/
MEDICINA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China