FAM83D inhibits autophagy and promotes proliferation and invasion of ovarian cancer cells via PI3K/AKT/mTOR pathway.
Acta Biochim Biophys Sin (Shanghai)
; 51(5): 509-516, 2019 May 23.
Article
en En
| MEDLINE
| ID: mdl-30939187
ABSTRACT
Ovarian cancer is one of the most lethal malignant tumors in women. The family with sequence similarity 83, member D (FAM83D) plays an important role in several cancers, but its function and underlying mechanism in ovarian cancer remain unknown. To investigate the role of FAM83D in ovarian cancer, the expression of FAM83D was determined by immunohistochemistry in tissue microarray slide. Cellular proliferation and invasion were detected by 5-Ethynyl-2'-deoxyuridine assays and transwell invasion assays. The correlations between FAM83D and autophagy were detected by western blot analysis and confocal microscopy. Western blot analysis was used to identify the protein expression of FAM83D, phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), mammalian target of rapamycin (mTOR) and Sequestosome 1 (P62). Tumorigenesis in nude mice was used to explore the function of FAM83D in vivo. We found high expression level of FAM83D in ovarian cancer tissues as compared to the normal ovarian tissues. Knockdown of FAM83D in SKOV3 cells enhanced autophagy and inhibited the proliferation and invasion in vitro, whereas ectopic expression of FAM83D in A2780 cells exerted an opposite effect. Mechanistically, overexpression of FAM83D activated the PI3K/AKT/mTOR pathway, and Torin1 could suppress FAM83D-induced cell proliferation and invasion. In vivo, overexpression FAM83D promoted tumor growth. Overall, FAM83D promoted ovarian cancer cell invasion and proliferation, while inhibited autophagy via the PI3K/AKT/mTOR signaling pathway. Our results suggest that FAM83D may be a candidate oncogene in ovarian cancer, which provides a fresh perspective of FAM83D in ovarian cancer.
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Banco de datos:
MEDLINE
Asunto principal:
Neoplasias Ováricas
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Autofagia
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Proteínas de Ciclo Celular
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Ensayos Antitumor por Modelo de Xenoinjerto
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Proliferación Celular
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Proteínas Asociadas a Microtúbulos
Límite:
Animals
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Female
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Humans
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Middle aged
Idioma:
En
Año:
2019
Tipo del documento:
Article