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Elevated TAK1 augments tumor growth and metastatic capacities of ovarian cancer cells through activation of NF-?B signaling.

ABSTRACT: Transforming growth factor (TGF)-?-activating kinase 1 (TAK1) is a serine/threonine kinase which is frequently associated with human cancer progression. However, its functional role in tumorigenesis is still controversial. Here, we report that TAK1 enhances the oncogenic capacity of ovarian cancer cells through the activation of NF-?B signaling. We found that TAK1 is frequently upregulated and significantly associated with high-grade and metastatic ovarian cancers. Mechanistic studies showed that Ser412 phosphorylation is required for TAK1 in activating NF-?B signaling and promotes aggressiveness of ovarian cancer cells. Conversely, suppression of TAK1 activity by point mutation at Ser412, RNAi mediated gene knockdown or TAK1 specific inhibitor ((5Z) -7-Oxozeaenol) remarkably impairs tumor growth and metastasis in ovarian cancer in vitro and in vivo. Our study underscores the importance of targeting TAK1 as a promising therapeutic approach to counteract the ovarian cancer progression.

SUBMITTER: Cai PC 

PROVIDER: S-EPMC4202143 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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Elevated TAK1 augments tumor growth and metastatic capacities of ovarian cancer cells through activation of NF-κB signaling.

Cai Patty C H PC   Shi Lei L   Liu Vincent W S VW   Tang Hermit W M HW   Liu Iris J IJ   Leung Thomas H Y TH   Chan Karen K L KK   Yam Judy W P JW   Yao Kwok-Ming KM   Ngan Hextan Y S HY   Chan David W DW  

Oncotarget 20140901 17

Transforming growth factor (TGF)-β-activating kinase 1 (TAK1) is a serine/threonine kinase which is frequently associated with human cancer progression. However, its functional role in tumorigenesis is still controversial. Here, we report that TAK1 enhances the oncogenic capacity of ovarian cancer cells through the activation of NF-κB signaling. We found that TAK1 is frequently upregulated and significantly associated with high-grade and metastatic ovarian cancers. Mechanistic studies showed tha  ...[more]

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