Loss of RAB25 Cooperates with Oncogenes in the Transformation of Human Mammary Epithelial Cells (HMECs) to Give Rise to Claudin-Low Tumors.
Biomed Res Int
; 2024: 8544837, 2024.
Article
en En
| MEDLINE
| ID: mdl-38803515
ABSTRACT
The loss of RAB25 expression-RAS superfamily of GTPase characteristic of numerous breast cancers-corresponds with H-RAS point mutations, particularly in triple-negative breast cancers (TNBC), a subtype associated with a poor prognosis. To address the poorly understood factors dictating the progression of TNBC tumors, we examine the cooperative effects that loss of RAB25 expression in human mammary epithelial cell (HMEC) lines with H-RAS mutations confers in tumorigenesis. HMECs were immortalized by transduction with LXSN CDK4 R24C, a mutant form of cyclin-dependent kinase, followed by transduction with hTERT, a catalytic subunit of the telomerase enzyme. We found that with the loss of RAB25 and overexpression of mutant H-RAS61L, immortal HMECs transformed toward anchorage-independent growth and acquired an increased ability to migrate. Furthermore, cells express low CD24, high CD44, and low claudin levels, indicating stem-like properties upon transformation. Besides, loss of RAB25 and overexpression of H-RAS61L resulted in increased expression of transcription factors Snail and Slug that drive these cells to lose E-cadherin and undergo epithelial-mesenchymal transition (EMT). This study confirms that loss of RAB25 and overexpression of mutant H-RAS can drive HMECs toward a mesenchymal stem-like state. Our findings reveal that RAB25 functions as a tumor suppressor gene, and loss of RAB25 could serve as a novel biomarker of the claudin-low type of TNBC.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Transformación Celular Neoplásica
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Proteínas de Unión al GTP rab
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Células Epiteliales
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Claudinas
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Transición Epitelial-Mesenquimal
Límite:
Female
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Humans
Idioma:
En
Revista:
Biomed Res Int
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos