Overexpression of MAP3K3 promotes tumour growth through activation of the NF-κB signalling pathway in ovarian carcinoma

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...

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Autores principales:	Ying Zhang, Sha-Sha Wang, Lin Tao, Li-Juan Pang, Hong Zou, Wei-Hua Liang, Zheng Liu, Su-Liang Guo, Jin-Fang Jiang, Wen-Jie Zhang, Wei Jia, Feng Li
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/71306ad817304110b9d1b3ce0fd7f3ed
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spelling	oai:doaj.org-article:71306ad817304110b9d1b3ce0fd7f3ed2021-12-02T15:09:33ZOverexpression of MAP3K3 promotes tumour growth through activation of the NF-κB signalling pathway in ovarian carcinoma10.1038/s41598-019-44835-72045-2322https://doaj.org/article/71306ad817304110b9d1b3ce0fd7f3ed2019-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-44835-7https://doaj.org/toc/2045-2322Abstract 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.Ying ZhangSha-Sha WangLin TaoLi-Juan PangHong ZouWei-Hua LiangZheng LiuSu-Liang GuoJin-Fang JiangWen-Jie ZhangWei JiaFeng LiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-13 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ying Zhang Sha-Sha Wang Lin Tao Li-Juan Pang Hong Zou Wei-Hua Liang Zheng Liu Su-Liang Guo Jin-Fang Jiang Wen-Jie Zhang Wei Jia Feng Li Overexpression of MAP3K3 promotes tumour growth through activation of the NF-κB signalling pathway in ovarian carcinoma
description	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.
format	article
author	Ying Zhang Sha-Sha Wang Lin Tao Li-Juan Pang Hong Zou Wei-Hua Liang Zheng Liu Su-Liang Guo Jin-Fang Jiang Wen-Jie Zhang Wei Jia Feng Li
author_facet	Ying Zhang Sha-Sha Wang Lin Tao Li-Juan Pang Hong Zou Wei-Hua Liang Zheng Liu Su-Liang Guo Jin-Fang Jiang Wen-Jie Zhang Wei Jia Feng Li
author_sort	Ying Zhang
title	Overexpression of MAP3K3 promotes tumour growth through activation of the NF-κB signalling pathway in ovarian carcinoma
title_short	Overexpression of MAP3K3 promotes tumour growth through activation of the NF-κB signalling pathway in ovarian carcinoma
title_full	Overexpression of MAP3K3 promotes tumour growth through activation of the NF-κB signalling pathway in ovarian carcinoma
title_fullStr	Overexpression of MAP3K3 promotes tumour growth through activation of the NF-κB signalling pathway in ovarian carcinoma
title_full_unstemmed	Overexpression of MAP3K3 promotes tumour growth through activation of the NF-κB signalling pathway in ovarian carcinoma
title_sort	overexpression of map3k3 promotes tumour growth through activation of the nf-κb signalling pathway in ovarian carcinoma
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/71306ad817304110b9d1b3ce0fd7f3ed
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Overexpression of MAP3K3 promotes tumour growth through activation of the NF-κB signalling pathway in ovarian carcinoma

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