PKP2 induced by YAP/TEAD4 promotes malignant progression of gastric cancer.
Mol Carcinog
; 63(9): 1654-1668, 2024 Sep.
Article
em En
| MEDLINE
| ID: mdl-38804704
ABSTRACT
Gastric cancer (GC) exhibits significant heterogeneity and its prognosis remains dismal. Therefore, it is essential to investigate new approaches for diagnosing and treating GC. Desmosome proteins are crucial for the advancement and growth of cancer. Plakophilin-2 (PKP2), a member of the desmosome protein family, frequently exhibits aberrant expression and is strongly associated with many tumor types' progression. In this study, we found upregulation of PKP2 in GC. Further correlation analysis showed a notable association between increased PKP2 expression and both tumor stage and poor prognosis in individuals diagnosed with gastric adenocarcinoma. In addition, our research revealed that the Yes-associated protein1 (YAP1)/TEAD4 complex could stimulate the transcriptional expression of PKP2 in GC. Elevated PKP2 levels facilitate activation of the AKT/mammalian target of rapamycin signaling pathway, thereby promoting the malignant progression of GC. By constructing a mouse model, we ultimately validated the molecular mechanism and function of PKP2 in GC. Taken together, these discoveries suggest that PKP2, as a direct gene target of YAP/TEAD4 regulation, has the potential to be used as an indication of GC progression and prognosis. PKP2 is expected to be a promising therapeutic target for GC.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias Gástricas
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Fatores de Transcrição
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Regulação Neoplásica da Expressão Gênica
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Progressão da Doença
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Proteínas Adaptadoras de Transdução de Sinal
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Proteínas de Ligação a DNA
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Placofilinas
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Proteínas de Sinalização YAP
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Fatores de Transcrição de Domínio TEA
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Proteínas Musculares
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article