Jupiter microtubule-associated homolog 1 (JPT1): A predictive and pharmacodynamic biomarker of metformin response in endometrial cancers.
Cancer Med
; 9(3): 1092-1103, 2020 02.
Article
en En
| MEDLINE
| ID: mdl-31808620
ABSTRACT
Preoperative use of metformin in obese women with endometrioid endometrial cancer (EEC) reduces tumor proliferation and inhibits the mammalian target of rapamycin pathway, though is only effective in select cases. This study sought to identify a predictive and/or pharmacodynamic proteomic signature of metformin response to tailor its pharmacologic use. Matched pre- and post-metformin-treated tumor tissues from a recently completed preoperative window trial of metformin in EEC patients (ClinicalTrials.gov NCT01911247) were analyzed by mass spectrometry (MS)-based proteomic and immunohistochemical analyses. Jupiter microtubule-associated homolog 1 (JPT1) was significantly elevated in metformin responders (n = 13) vs nonresponders (n = 7), and found to decrease in abundance in metformin responders following treatment; observations that were verified by immunohistochemical staining for JPT1. Metformin response and loss of JPT1 were assessed in RL95-2 and ACI-181 endometrial cancer (EC) cell lines. We further identified that silencing of JPT1 abundance does not alter cellular response to metformin or basal cell proliferation, but that JPT1 abundance does decrease in response to metformin treatment in RL95-2 and ACI-181 EC cell lines. These data suggest that JPT1 represents a predictive and pharmacodynamic biomarker of metformin response that, if validated in larger patient populations, may enable preoperative EEC patient stratification to metformin treatment and the ability to monitor patient response.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Biomarcadores de Tumor
/
Neoplasias Endometriales
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Carcinoma Endometrioide
/
Proteínas de Ciclo Celular
/
Metformina
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Proteínas Asociadas a Microtúbulos
/
Obesidad
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Adolescent
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Adult
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Aged
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Female
/
Humans
/
Middle aged
Idioma:
En
Revista:
Cancer Med
Año:
2020
Tipo del documento:
Article
País de afiliación:
Estados Unidos