The GEF-H1/PKD3 signaling pathway promotes the maintenance of triple-negative breast cancer stem cells.
Int J Cancer
; 146(12): 3423-3434, 2020 06 15.
Article
em En
| MEDLINE
| ID: mdl-31745977
ABSTRACT
Protein kinase D3 (PKD3) is upregulated in triple-negative breast cancer (TNBC) and associated with cell proliferation and metastasis development but its precise pro-oncogenic function is unknown. Here we show that PKD3 is required for the maintenance of the TNBC stem cell population. The depletion of PKD3 in MDA-MB-231 cells reduced the cancer stem cell frequency in vitro and tumor initiation potential in vivo. We further provide evidence that the RhoGEF GEF-H1 is upstream of PKD3 activation in TNBC stem cells. Most importantly, pharmacological PKD inhibition in combination with paclitaxel synergistically decreased oncosphere and colony formation efficiency in vitro and tumor recurrence in vivo. Based on our results we propose that targeting the GEF-H1/PKD3 signaling pathway in combination with chemotherapy might provide an effective therapeutic option for TNBC.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco Neoplásicas
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Proteína Quinase C
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Protocolos de Quimioterapia Combinada Antineoplásica
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Neoplasias de Mama Triplo Negativas
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Fatores de Troca de Nucleotídeo Guanina Rho
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Female
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Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article