Overexpression of MAP3K3 promotes tumour growth through activation of the NF-κB signalling pathway in ovarian carcinoma
Overexpression of MAP3K3 promotes tumour growth through activation of the NF-κB signalling pathway in ovarian carcinoma
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卵巢癌中 MAP3K3 的过表达通过激活 NF-κB 信号通路促进肿瘤生长
DOI：
10.1038/s41598-019-44835-7
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发表时间：
2019-06
影响因子：
4.6
通讯作者：
Li Feng
中科院分区：
文献类型：
--
作者：
Zhang Ying;Wang Shasha;Tao Lin;Pang Lijuan;Zou Hong;Liang Weihua;Liu Zheng;Guo Suliang;Jiang Jinfang;Zhang Wenjie;Jia Wei;Li Feng
丝裂原活化蛋白激酶激酶激酶3（MAP 3 K3）是丝氨酸/苏氨酸蛋白激酶家族的成员，广泛表达并作为癌基因起作用。然而，MAP 3 K3在卵巢癌中的表达及其确切的分子机制尚不清楚。在此，我们发现MAP 3 K3蛋白在70.5%的高级别浆液性卵巢癌（HGSOC）样本中高表达。MAP 3 K3过表达与FIGO分期和化疗反应显著相关。体外实验表明，MAP 3 K3过表达促进OC细胞增殖，抑制凋亡，增强OC细胞的迁移和侵袭能力。此外，体内肿瘤发生实验证实，沉默MAP 3 K3显著降低了裸鼠移植肿瘤的生长速率和体积。药物敏感性实验表明，MAP 3 K3在OC细胞系中的差异表达与化疗耐药性相关。在功能上，MAP 3 K3基因通过介导NF-κB信号通路，影响下游上皮-间质转化和细胞骨架蛋白的表达，从而调控OC细胞的恶性生物学行为。我们的研究结果揭示了MAP 3 K3在介导NF-κB信号传导中的作用，以促进OC细胞的增殖、侵袭、迁移和化疗耐药性，突出了潜在的新的治疗和预后靶点。
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 vitroexperiments showed that MAP3K3 overexpression promoted cell proliferation, inhibited apoptosis, and enhanced the migration and invasion of OC cells. Moreover,in vivotumourigenesis 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.
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DOI：
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发表时间：
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期刊：
The Journal of biological chemistry
影响因子：
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10.3410/f.734004835.793572727
发表时间：
2020-03
期刊：
Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature
影响因子：
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DOI：
10.3410/f.734004835.793574878
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2020-05
期刊：
Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature
影响因子：
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