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Anticancer Res ; 41(12): 5959-5971, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34848450

RESUMEN

BACKGROUND/AIM: We examined the inhibitory effects of both glyoxalase 1 (GLO 1) and protein kinase C (PKC)λ in aldehyde dehydrogenase 1 (ALDH1)-positive breast cancer stem cells (CSCs). MATERIALS AND METHODS: Breast cancer genomics datasets (TCGA, n=593; METABRIC, n=1904) were downloaded and statistically analyzed. The effects of GLO 1 and PKCλ on trypan blue staining and tumor-sphere formation by ALDH1high cells derived from triple negative breast cancer (TNBC) and basal-like breast cancer were examined. RESULTS: GLO 1high, PKCλhigh, and ALDH1A3high tumors were enriched in stage I/II/III/IV samples, associated with the HER2 and TNBC subtypes according to receptor status, and associated with the HER2-enriched and basal-like subtypes according to PAM50. Inhibition of either GLO 1 (TLSC702) or PKCλ (ANF) suppressed tumor-sphere formation and enhanced death in ALDH1high cells. TLSC702 also effectively inhibited tumor-sphere formation and induced death in PKCλ knockout ALDH1high cells. CONCLUSION: GLO 1 and PKCλ are important for the survival of ALDH1-positive breast CSCs, and may represent potential therapeutic targets for the treatment of ALDH1-positive breast CSCs.


Asunto(s)
Familia de Aldehído Deshidrogenasa 1/metabolismo , Neoplasias de la Mama/metabolismo , Isoenzimas/metabolismo , Lactoilglutatión Liasa/metabolismo , Células Madre Neoplásicas/metabolismo , Proteína Quinasa C/metabolismo , Familia de Aldehído Deshidrogenasa 1/genética , Biomarcadores de Tumor , Neoplasias de la Mama/etiología , Neoplasias de la Mama/patología , Línea Celular Tumoral , Supervivencia Celular , Femenino , Citometría de Flujo , Perfilación de la Expresión Génica , Humanos , Estadificación de Neoplasias , Células Madre Neoplásicas/patología , Transcriptoma
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