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Loss of PDZK1 expression activates PI3K/AKT signaling via PTEN phosphorylation in gastric cancer

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收录情况： ◇ SCIE

作者：
Zhao, Chunjuan[1] * ; Tao, Tao[1] * ; Yang, Longyan[2] * ; Qin, Qiong[1,*2] ; Wang, Ying[1] ; Liu, Hua[1] ; Song, Ran[1] ; Yang, Xiaomei[1] ; Wang, Qiqi[1] ; Gu, Siyu[1] ; Xiong, Ying[1] ; Zhao, Dong[2] ; Wang, Songlin[1] ; Feng, Duiping[3] ; Jiang, Wen G.[4] ; Zhang, Jun[5,*3] ; He, Junqi[1,*1] ;
单位： [1]Beijing Key Laboratory for Tumor Invasion and Metastasis, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, 100069, Beijing, China [2]Department of Endocrinology, Beijing Luhe Hospital, Capital Medical University, 101149, Beijing, China [3]Department of Interventional Radiology, First Hospital of Shanxi Medical University, 030001, Taiyuan, China [4]Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Health Park, Cardiff, CF14 4XN, UK [5]Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, 100050, Beijing, China
出处：
DOI： 10.1016/j.canlet.2019.03.043
ISSN：

关键词： NHERF3 PTEN Gastric cancer Phosphorylation PDZ Carcinogenesis

摘要：
Phosphorylation of PTEN plays an important role in carcinogenesis and progression of gastric cancer. However, the underlying mechanism of PTEN phosphorylation regulation remains largely elusive. In the present study, PDZK1 was identified as a novel binding protein of PTEN by association of PTEN through its carboxyl terminus and PDZ domains of PDZK1. By direct interaction with PTEN, PDZK1 inhibited the phosphorylation of PTEN at S380/T382/T383 cluster and further enhanced the capacity of PTEN to suppress PI3K/AKT activation. PDZK1 suppressed gastric cancer cell proliferation by diminishing PI3K/AKT activation via inhibition of PTEN phosphorylation in vitro and in vivo. The expression of PDZK1 was frequently downregulated in gastric cancer specimens and correlated with progression and poor prognosis of gastric cancer patients. Downregulation of PDZK1 was associated with PTEN inactivation, AKT signaling and cell proliferation activation in clinical specimens. Thus, low levels of PDZK1 in gastric cancer specimens lead to increase proliferation of gastric cancer cells via phosphorylation of PTEN at the S380/T382/T383 cluster and constitutively activation of PI3K/AKT signaling, which results in poor prognosis of gastric cancer patients.

基金：
National Natural Science Foundation of the People's Republic of ChinaNational Natural Science Foundation of China (NSFC) [81572333, 81772707, 81472409]; Beijing Municipal Natural Science FoundationBeijing Natural Science Foundation [7192020, 7182016, 7152014]; Beijing Natural Science Foundation ProgramBeijing Natural Science Foundation [KZ201710025015]; Scientific Research Key Program of Beijing Municipal Commission of EducationBeijing Municipal Commission of Education [KZ201710025015]; Support Project of High-level Teachers in Beijing Municipal Universities in the Period of 13th Five-year Plan [IDHT29170516]
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外文
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出版当年[2018]版：
大类 | 1 区 医学
小类 | 2 区 肿瘤学
最新[2025]版：
大类 | 1 区 医学
小类 | 2 区 肿瘤学
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出版当年[2017]版：
Q1 ONCOLOGY
最新[2023]版：
Q1 ONCOLOGY

影响因子： 最新[2023版] 最新五年平均[2021-2025] 出版当年[2017版] 出版当年五年平均[2013-2017] 出版前一年[2016版] 出版后一年[2018版]

第一作者：
第一作者单位： [1]Beijing Key Laboratory for Tumor Invasion and Metastasis, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, 100069, Beijing, China
共同第一作者：
通讯作者：
通讯机构： [1]Beijing Key Laboratory for Tumor Invasion and Metastasis, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, 100069, Beijing, China [5]Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, 100050, Beijing, China [*1]Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, No.10 Xitoutiao, You An Men, Beijing, 100069, PR China. [*2]Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, No.10 Xitoutiao, You An Men, Beijing, 100069, PR China. [*3]Department of General Surgery, Beijing Friendship Hospital, Beijing, 100050, China
推荐引用方式(GB/T 7714)：
Zhao Chunjuan,Tao Tao,Yang Longyan,et al.Loss of PDZK1 expression activates PI3K/AKT signaling via PTEN phosphorylation in gastric cancer[J].CANCER LETTERS.2019,453:107-121.doi:10.1016/j.canlet.2019.03.043.
APA：
Zhao, Chunjuan,Tao, Tao,Yang, Longyan,Qin, Qiong,Wang, Ying...&He, Junqi.(2019).Loss of PDZK1 expression activates PI3K/AKT signaling via PTEN phosphorylation in gastric cancer.CANCER LETTERS,453,
MLA：
Zhao, Chunjuan,et al."Loss of PDZK1 expression activates PI3K/AKT signaling via PTEN phosphorylation in gastric cancer".CANCER LETTERS 453.(2019):107-121

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