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  2. Identification of TGF-β-activated kinase 1 as a possible novel target for renal cell carcinoma intervention

Identification of TGF-β-activated kinase 1 as a possible novel target for renal cell carcinoma intervention

  • Biochem Biophys Res Commun. 2014 Oct 10;453(1):106-11. doi: 10.1016/j.bbrc.2014.09.070.
Fandong Meng 1 Yan Li 1 Xin Tian 1 Liye Fu 1 Yuanqin Yin 1 Chengguang Sui 1 Ping Ma 1 Youhong Jiang 2
Affiliations

Affiliations

  • 1 Molecular Oncology Department of Cancer Research Institution, The First Hospital of China Medical University, Shengyang, Liaoning City 110001, China.
  • 2 Molecular Oncology Department of Cancer Research Institution, The First Hospital of China Medical University, Shengyang, Liaoning City 110001, China. Electronic address: [email protected].
Abstract

Renal cell carcinoma (RCC) is common renal malignancy within poor prognosis. TGF-β-activated kinase 1 (TAK1) plays vital roles in cell survival, apoptosis-resistance and carcinogenesis through regulating nuclear factor-κB (NF-κB) and other cancer-related pathways. Here we found that TAK1 inhibitors (LYTAK1, 5Z-7-oxozeanol (5Z) and NG-25) suppressed NF-κB activation and RCC cell (786-O and A489 lines) survival. TAK1 inhibitors induced apoptotic cytotoxicity against RCC cells, which was largely inhibited by the broad or specific Caspase inhibitors. Further, shRNA-mediated partial depletion of TAK1 reduced 786-O cell viability whiling activating Apoptosis. Significantly, TAK1 was over-expressed in human RCC tissues, and its level was correlated with phosphorylated NF-κB. Finally, kinase inhibition or genetic depletion of TAK1 enhanced the activity of vinblastine sulfate (VLB) in RCC cells. Together, these results suggest that TAK1 may be an important oncogene or an effective target for RCC intervention.

Keywords

Apoptosis and chemo-resistance; NF-κB activation; Renal cell carcinoma (RCC); TGF-β-activated kinase 1 (TAK1).

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