Prognostic and therapeutic relevance of phosphofructokinase platelet-type (PFKP) in breast cancer.
Exp Cell Res
; 396(1): 112282, 2020 11 01.
Article
em En
| MEDLINE
| ID: mdl-32919954
ABSTRACT
In the present study, we have explored the prognostic value of the Phosphofructokinase Platelet-type (PFKP) expression and its therapeutic relevance in metastatic breast cancer. PFKP immunohistochemistry was performed on Invasive ductal carcinomas (IDCs; n = 87) of breast, and its association with clinicopathological parameters were evaluated. Using online meta-analysis tools, PFKP's prognostic value was investigated in overall breast cancer as well as in triple negative subtype (TNBCs). For in vitro analysis, MDA-MB-231 cells model was used in order to elucidate mechanisms behind PFKP regulated glycolysis and its impact on cancer cell physiology. Therapeutic relevance of PFKP was further evaluated using PFKP siRNA and Quercetin. PFKP protein expression was found to be positively associated with nodal invasion (p = 0.009), receptor (ER & PR) negative status (p = 0.005 & p = 0.028) and reduced overall survival in breast cancer patients (p = 0.014). In MDA-MB-231 cells, quercetin treatment impaired PFKP-LDHA signaling axis thereby inhibiting aerobic glycolysis mediated increased migration of cancer cells. Our present study demonstrates that elevated PFKP levels are associated with basal cells/TNBC subtypes and might serve as prognostic indicator for TNBC patients. Ability of quercetin to inhibit aerobic glycolysis, cell migration and clonogenic potential of malignant breast cancer cells advocates possibility of quercetin in aggressive breast cancer treatment.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
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Regulação Neoplásica da Expressão Gênica
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Carcinoma Ductal de Mama
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Fosfofrutoquinase-1 Tipo C
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Neoplasias de Mama Triplo Negativas
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L-Lactato Desidrogenase
Tipo de estudo:
Diagnostic_studies
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Prognostic_studies
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Systematic_reviews
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article