PTEN overexpression and nuclear ß-catenin stabilization promote morular differentiation through induction of epithelial-mesenchymal transition and cancer stem cell-like properties in endometrial carcinoma.
Cell Commun Signal
; 20(1): 181, 2022 11 21.
Article
em En
| MEDLINE
| ID: mdl-36411429
ABSTRACT
BACKGROUND:
Although a lack of functional PTEN contributes to tumorigenesis in a wide spectrum of human malignancies, little is known about the functional role of its overexpression in the tumors. The current study focused on PTEN overexpression in endometrial carcinoma (Em Ca).METHODS:
The functional impact of PTEN overexpression was assessed by Em Ca cell lines. Immunohistochemical analyses were also conducted using 38 Em Ca with morular lesions.RESULTS:
Em Ca cell lines stably overexpressing PTEN (H6-PTEN) exhibited epithelial-mesenchymal transition (EMT)-like features, probably through ß-catenin/Slug-meditated suppression of E-cadherin. PTEN overexpression also inhibited cell proliferation, accelerated cellular senescence, increased apoptotic features, and enhanced migration capability. Moreover, H6-PTEN cells exhibited cancer stem cell (CSC)-like properties, along with high expression of aldehyde dehydrogenase 1 and CD44s, a large ALDH 1high population, enriched spheroid formation, and ß-catenin-mediated upregulation of cyclin D2, which is required for persistent CSC growth. In clinical samples, immunoreactivities for PTEN, as well as CSC-related molecules, were significantly higher in morular lesions as compared to the surrounding carcinomas. PTEN score was positively correlated with expression of nuclear ß-catenin, cytoplasmic CD133, and CD44v6, and negatively with cell proliferation. Finally, estrogen receptor-α (ERα)-dependent expression of Ezrin-radixin-moesin-binding phophoprotein-50 (EBP50), a multifunctional scaffolding protein, acts as a negative regulator of morular formation by Em Ca cells through interacting with PTEN and ß-catenin.CONCLUSION:
In the abscess of ERα/EBP50 expression, PTEN overexpression and nuclear ß-catenin stabilization promote the establishment and maintenance of morular phenotype associated with EMT/CSC-like features in Em Ca cells. Video Abstract.Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Neoplasias do Endométrio
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PTEN Fosfo-Hidrolase
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Cell Commun Signal
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Japão