Inhibition of TPL2 by interferon- suppresses bladder cancer through activation of PDE4D
文献类型：期刊论文
| 作者 | Qiang, Zhe2,6; Zhou, Zong-yuan2,6; Peng,Ting2,6; Jiang, Pu-zi3; Shi, Nan2,6; Njoya,Emmanuel Mfotie2,5; Azimova, Bahtigul2; Liu, Wan-li4; Chen, Wei-hua1,3; Zhang, Guo-lin2 |
| 刊名 | JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
 |
| 出版日期 | 2019-11-27 |
| 卷号 | 37页码:288 |
| ISSN号 | 1756-9966 |
| 关键词 | Interferon TPL2 PDE4D cAMP COX-2 |
| DOI | 10.1186/s13046-018-0971-4 |
| 产权排序 | 1 |
| 文献子类 | Article |
| 英文摘要 | BackgroundDrugs that inhibit the MEK/ERK pathway have therapeutic benefit in bladder cancer treatment but responses vary with patients, for reasons that are still not very clear. Interferon- (IFN-) is also used as a therapeutic agent for bladder cancer treatment but the response rate is low. It was found that IFN- could enhance the cytotoxic effect of MEK inhibition. However, the potential mechanisms of that are still unclear. Understanding of the cross-talk between the IFN- and MEK/ERK pathway will help enhance the efficacy of IFN- or MEK inhibitors on bladder cancer.MethodsImmunoprecipitation and pull-down assay were used to reveal the formation of signaling complex. The protein expressions were detected by western blot and immunohistochemistry. The cAMP level, Phosphodiesterase 4D (PDE4D) activity and Prostaglandin E-2 (PGE(2)) concentration in cells, serum and tissues were detected by enzyme-linked immunosorbent assay. The role of PDE4D in bladder tumorigenesis in vivo was examined by the xenograft model. Tissue microarray chips were used to investigate the prognostic roles of PDE4D and tumor progression locus 2 (TPL2) in bladder cancer patients.ResultsIFN- down-regulated the cyclooxygenase-2 (COX-2) expression in bladder cancer cells through the inhibition of TPL2/NF-B pathway; IFN- also inhibited COX-2 expression by suppressing cAMP signaling through TPL2-ERK mediated PDE4D activity. Reduction of the intracellular cAMP level by PDE4D potentiated the antitumor effect of IFN- against bladder cancer in vitro and in vivo. Further analysis of clinical samples indicated that low PDE4D expression and high level of TPL2 phosphorylation were correlated to the development and poor prognosis in bladder cancer patients.ConclusionsOur data reveal that IFN- can exert its antitumor effect through a non-canonical JAK-STAT pathway in the bladder cancer cells with low activity of IFN pathway, and the TPL2 inhibition is another function of IFN- in the context of bladder cancer therapy. The antitumor effects of IFN- and MEK inhibition also depend on the PDE4D-mediated cAMP level in bladder cancer cells. Suppression of the TPL2 phosphorylation and intracellular cAMP level may be possible therapeutic strategies for enhancing the effectiveness of IFN- and MEK inhibitors in bladder cancer treatment. |
| 学科主题 | Oncology |
| URL标识 | 查看原文 |
| WOS关键词 | MAP KINASE ; ALPHA SUPPRESSES ; PROSTATE-CANCER ; CROSS-TALK ; IN-VITRO ; CAMP ; INDUCTION ; PATHWAY ; PKA ; PHOSPHORYLATION |
| WOS研究方向 | Oncology |
| 语种 | 英语 |
| 出版者 | BMC |
| WOS记录号 | WOS:000451436500003 |
| 源URL | [http://210.75.237.14/handle/351003/30105]  |
| 专题 | 国家天然药物工程技术研究中心_天然产物研究 国家天然药物工程技术研究中心_天然药物与临床转化重点实验室 |
| 作者单位 | 1.Henan Normal Univ, Coll Life Sci, Xinxiang, Peoples R China; 2.Chinese Acad Sci, Chengdu Inst Biol, Key Lab Nat Med & Clin Translat, Chengdu, Sichuan, Peoples R China; 3.Huazhong Univ Sci & Technol, Hubei Key Lab Bioinformat & Mol Imaging, Coll Life Sci & Technol, Key Lab Mol Biophys,Minist Educ,Dept Bioinformat, Wuhan, Hubei, Peoples R China; 4.Tsinghua Univ, Sch Life Sci, Minist Educ, Key Lab Prot Sci, Beijing, Peoples R China; 5.Univ Yaounde I, Dept Biochem, Fac Sci, Yaounde, Cameroon; 6.Univ Chinese Acad Sci, Beijing, Peoples R China |
| 推荐引用方式 GB/T 7714 | Qiang, Zhe,Zhou, Zong-yuan,Peng,Ting,et al. Inhibition of TPL2 by interferon- suppresses bladder cancer through activation of PDE4D[J]. JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH,2019,37:288. |
| APA | Qiang, Zhe.,Zhou, Zong-yuan.,Peng,Ting.,Jiang, Pu-zi.,Shi, Nan.,...&Wang, Fei.(2019).Inhibition of TPL2 by interferon- suppresses bladder cancer through activation of PDE4D.JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH,37,288. |
| MLA | Qiang, Zhe,et al."Inhibition of TPL2 by interferon- suppresses bladder cancer through activation of PDE4D".JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH 37(2019):288. |
入库方式： OAI收割
来源：成都生物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。