Lemur tyrosine kinase 2 acts as a positive regulator of NF-kappa B activation and colon cancer cell proliferation
文献类型：期刊论文
| 作者 | Zhang, Rongjing3; Li, Xiuxiu3; Qin, Yanqing3; Wei, Lumin4; Fang, Jing1,2; , |
| 刊名 | CANCER LETTERS
 |
| 出版日期 | 2019 |
| 卷号 | 454期号:-页码:70-77 |
| 关键词 | LMTK2 NF-kappa B Colon cancer |
| ISSN号 | 0304-3835 |
| DOI | 10.1016/j.canlet.2019.04.011 |
| 文献子类 | Article |
| 英文摘要 | Lemur tyrosine kinase 2 (LMTK2) belongs to both protein kinase and tyrosine kinase families. LMTK2 is less studied and little is known about its function. Here we demonstrate that LMTK2 modulates NF-kappa B activity and functions to promote colonic tumorigenesis. We found that LMTK2 protein was abundant in colon cancer cells and LMTK2 knockdown (LMTK2-KD) inhibited proliferation of colon cancer cells through inactivating NF-kappa B. In unstimulated condition, LMTK2 modulated NF-kappa B through inhibiting phosphorylation of p65 at Ser468. Mechanistically, LMTK2 phosphorylated protein phosphatase 1A (PP1A) to prevent PP1A from dephosphorylating p-GSK3 beta(Ser9). The p-GSK3 beta(Ser9) could not phosphorylate p65 at Ser468, which maintained the basal NF-kappa B activity. LMTK2 also modulated TNF alpha-activated NF-kappa B. LMTK2-KD repressed TNF alpha-induced IKK beta phosphorylation, I kappa B alpha degradation and NF-kappa B activation, implying that LMTK2 modulates TNF alpha-activated NF-kappa B via UGC These results suggest that LMTK2 modulates basal and TNF alpha-induced NF-kappa B activities in different mechanisms. Animal studies show that LMTK2-KD suppressed colon cancer cell xenograft growth, decreased PP1A phosphorylation and increased p-p65(Ser468). Our results reveal the role and underlying mechanism of LMTK2 in colonic tumorigenesis and suggest that LMTK2 may serve as a potential target for chemotherapy of colon cancer. |
| 学科主题 | Oncology |
| WOS关键词 | CYCLIN D1 ; MYOSIN-VI ; IKK-BETA ; PROTEIN ; PHOSPHORYLATION ; PHOSPHATASE ; BINDING ; GROWTH ; P65 ; EXPRESSION |
| 语种 | 英语 |
| WOS记录号 | WOS:000468255000008 |
| 出版者 | ELSEVIER IRELAND LTD |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/612]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所 |
| 作者单位 | 1.Qingdao Univ, Affiliated Hosp, Inst Canc, Qingdao 266061, Shandong, Peoples R China; 2.Qingdao Univ, Inst Canc, Qingdao 266061, Shandong, Peoples R China, 3.Univ Chinese Acad Sci, Chinese Acad Sci, CAS Key Lab Nutr Metab & Food Safety, Shanghai Inst Nutr & Hlth,Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China; 4.Shanghai Jiao Tong Univ, Ruijin Hosp, Shanghai 200025, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Zhang, Rongjing,Li, Xiuxiu,Qin, Yanqing,et al. Lemur tyrosine kinase 2 acts as a positive regulator of NF-kappa B activation and colon cancer cell proliferation[J]. CANCER LETTERS,2019,454(-):70-77. |
| APA | Zhang, Rongjing,Li, Xiuxiu,Qin, Yanqing,Wei, Lumin,Fang, Jing,&,.(2019).Lemur tyrosine kinase 2 acts as a positive regulator of NF-kappa B activation and colon cancer cell proliferation.CANCER LETTERS,454(-),70-77. |
| MLA | Zhang, Rongjing,et al."Lemur tyrosine kinase 2 acts as a positive regulator of NF-kappa B activation and colon cancer cell proliferation".CANCER LETTERS 454.-(2019):70-77. |
入库方式： OAI收割
来源：上海营养与健康研究所
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