Overexpression of MAP3K3 promotes tumour growth through activation of the NF-κB signalling pathway in ovarian carcinoma.
Sci Rep
; 9(1): 8401, 2019 06 10.
Article
en En
| MEDLINE
| ID: mdl-31182739
ABSTRACT
Mitogen-activated protein kinase kinase kinase 3 (MAP3K3), a member of the serine/threonine protein kinase family, is ubiquitously expressed and acts as an oncogene. However, the expression and exact molecular mechanism of MAP3K3 in ovarian carcinoma (OC) remain unclear. Here, we found that MAP3K3 protein was highly expressed in 70.5% of high-grade serous ovarian carcinoma (HGSOC) samples. MAP3K3 overexpression was significantly associated with the FIGO stage and chemotherapy response. Additionally, MAP3K3 overexpression was associated with reduced disease-free survival and overall survival. In vitro experiments showed that MAP3K3 overexpression promoted cell proliferation, inhibited apoptosis, and enhanced the migration and invasion of OC cells. Moreover, in vivo tumourigenesis experiments confirmed that silencing MAP3K3 significantly reduced the growth rate and volume of transplanted tumours in nude mice. Drug sensitivity experiments demonstrated that differential expression of MAP3K3 in OC cell lines correlates with chemotherapy resistance. Functionally, the MAP3K3 gene regulated the malignant biological behaviour of OC cells by mediating NF-κB signalling pathways, affecting the downstream epithelial-mesenchymal transition and cytoskeletal protein expression. Our results unveiled the role of MAP3K3 in mediating NF-κB signalling to promote the proliferation, invasion, migration, and chemotherapeutic resistance of OC cells, highlighting a potential new therapeutic and prognostic target.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Ováricas
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FN-kappa B
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MAP Quinasa Quinasa Quinasa 3
Tipo de estudio:
Etiology_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Sci Rep
Año:
2019
Tipo del documento:
Article
País de afiliación:
China