title: Identification of TGF-β-activated kinase 1 as a possible novel target for renal cell carcinoma intervention.
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.
authors.affiliation: Molecular Oncology Department of Cancer Research Institution, The First Hospital of China Medical University, Shengyang, Liaoning City 110001, China.
authors.forename: Fandong
authors.initials: F
authors.lastname: Meng
authors.affiliation: Molecular Oncology Department of Cancer Research Institution, The First Hospital of China Medical University, Shengyang, Liaoning City 110001, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Molecular Oncology Department of Cancer Research Institution, The First Hospital of China Medical University, Shengyang, Liaoning City 110001, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Tian
authors.affiliation: Molecular Oncology Department of Cancer Research Institution, The First Hospital of China Medical University, Shengyang, Liaoning City 110001, China.
authors.forename: Liye
authors.initials: L
authors.lastname: Fu
authors.affiliation: Molecular Oncology Department of Cancer Research Institution, The First Hospital of China Medical University, Shengyang, Liaoning City 110001, China.
authors.forename: Yuanqin
authors.initials: Y
authors.lastname: Yin
authors.affiliation: Molecular Oncology Department of Cancer Research Institution, The First Hospital of China Medical University, Shengyang, Liaoning City 110001, China.
authors.forename: Chengguang
authors.initials: C
authors.lastname: Sui
authors.affiliation: Molecular Oncology Department of Cancer Research Institution, The First Hospital of China Medical University, Shengyang, Liaoning City 110001, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Ma
authors.affiliation: Molecular Oncology Department of Cancer Research Institution, The First Hospital of China Medical University, Shengyang, Liaoning City 110001, China. Electronic address: youyuanhongyeah@yeah.net.
authors.forename: Youhong
authors.initials: Y
authors.lastname: Jiang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002292:Carcinoma, Renal Cell / Q000201:enzymology* / Q000235:genetics / Q000628:therapy; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D055785:Gene Knockdown Techniques; D006801:Humans; D007680:Kidney Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000628:therapy; D007783:Lactones / Q000494:pharmacology; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009857:Oncogenes; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D012118:Resorcinols / Q000494:pharmacology; D014410:Tumor Stem Cell Assay; D015854:Up-Regulation; D014747:Vinblastine / Q000494:pharmacology; D000099151:MAP Kinase Kinase Kinase 7; D015025:Zearalenone / Q000008:administration & dosage
chemical_list: D007783:Lactones; D020930:MAP Kinase Kinase Kinases; D016328:NF-kappa B; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D034741:RNA, Small Interfering; D012118:Resorcinols; D014747:Vinblastine; D000099151:MAP Kinase Kinase Kinase 7; C505734:7-oxozeanol; D015025:Zearalenone
keywords: Apoptosis and chemo-resistance; NF-κB activation; Renal cell carcinoma (RCC); TGF-β-activated kinase 1 (TAK1)