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Inhibiting ALK-TOPK signaling pathway promotes cell apoptosis of ALK-positive NSCLC

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收录情况： ◇ SCIE

作者：
Xiao Juanjuan[1,2,3] * ; Zhang Lu[4] * ; Yi Huijun[1] ; Zou Ling[3] ; Mo Jianmei[1,2] ; Xue Feng[5,13] ; Zheng Jinhua[6] ; Huang Yingze[1,2] ; Lu Hui[7] ; Wu Hansheng[8,9,10] ; Xue Peipei[11] ; Zhang Xin[5] ; He Lifei[1,2] ; Li Zhaoxin[1,2] ; Pang Shigui[1,2] ; Qiao Guibin[9,10] ; Duan Qiuhong[3] ; Zhu Feng[1,2,12] ;
机构： [1]Cancer Research Institute, The Affiliated Hospital of Guilin Medical University, Guilin 541001 Guangxi, People’s Republic of China [2]Guangxi Health Commission Key Laboratory of Novel Onco-Kinases in Target Therapy, The Affiliated Hospital of Guilin Medical University, 541001 Guilin, Guangxi, People’s Republic of China [3]Department of Biochemistry and Molecular Biology, School of Basic Medicine, Huazhong University of Science and Technology, 430030 Wuhan, Hubei, People’s Republic of China [4]The Fifth Clinical Medical College of Henan University of Chinese Medicine (Zhengzhou People’s Hospital), 450053 Zhengzhou, Henan, People’s Republic of China [5]Department of Oncology, The AffiliatedHospital of Guilin Medical University, 541001 Guilin, Guangxi, People’s Republic of China [6]Department of Pathology, The Affiliated Hospital of Guilin Medical University, 541001Guilin, Guangxi, People’s Republic of China [7]Wuhan Children’s Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Scienceand Technology, 430015 Wuhan, Hubei, People’s Republic of China [8]Department of Thoracic Surgery, The first affiliated hospital of Shanton University Medical College, 515041 Shantou, Guangdong, People’s Republic of China [9]Department of Thoracic Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, 510080Guangzhou, People’s Republic of China [10]The Second School of Clinical Medicine, Southern Medical University, 510515 Guangzhou, People’s Republic of China [11]NHC Key Laboratory of Birth Defects and Reproductive Health, Chongqing Population and Family Planning Science and Technology Research Institute, 400000 Chongqing, People’sRepublic of China [12]Guangxi Key Laboratory of Molecular Medicine in Liver Injury and Repair, the Affiliated Hospital of Guilin Medical University, 541001 Guilin, Guangxi, People’sRepublic of China [13]Present address: Guangxi Health Commission Key Laboratory of Novel Onco-Kinases in Target Therapy, The Affiliated Hospital of Guilin Medical University,541001 Guilin, Guangxi, People’s Republic of China
出处：
DOI： 10.1038/s41419-022-05260-3
ISSN：

摘要：
T-LAK cell-oriented protein kinase (TOPK) is a potential therapeutic target in tumors. However, its role in anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) has not been reported. Here, we found that TOPK was highly expressed in ALK-positive NSCLC. Additionally, ALK was identified as another upstream kinase of TOPK by in vitro kinase assay screening. Then, it was proven that ALK phosphorylated TOPK at Y74 in vitro and ex vivo, and the pathways downstream of ALK-TOPK were explored by phosphoproteomic analysis. Subsequently, we demonstrated that inhibiting TOPK enhanced tumor sensitivity to alectinib (an ALK inhibitor). The combination of alectinib and HI-032 (a TOPK inhibitor) suppressed the growth and promoted the apoptosis of ALK-positive NSCLC cells ex vivo and in vivo. Our findings reveal a novel ALK-TOPK signaling pathway in ALK-positive NSCLC. The combination of alectinib and HI-032 might be a promising therapeutic strategy for improving the sensitivity of ALK-positive NSCLC to targeted therapy.© 2022. The Author(s).

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出版当年[2021]版：
大类 | 1 区 生物学
小类 | 2 区 细胞生物学
最新[2025]版：
大类 | 1 区 生物学
小类 | 2 区 细胞生物学
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出版当年[2020]版：
Q1 CELL BIOLOGY
最新[2023]版：
Q1 CELL BIOLOGY

影响因子： 最新[2023版] 最新五年平均 出版当年[2020版] 出版当年五年平均 出版前一年[2019版] 出版后一年[2021版]

第一作者：
第一作者机构： [1]Cancer Research Institute, The Affiliated Hospital of Guilin Medical University, Guilin 541001 Guangxi, People’s Republic of China [2]Guangxi Health Commission Key Laboratory of Novel Onco-Kinases in Target Therapy, The Affiliated Hospital of Guilin Medical University, 541001 Guilin, Guangxi, People’s Republic of China [3]Department of Biochemistry and Molecular Biology, School of Basic Medicine, Huazhong University of Science and Technology, 430030 Wuhan, Hubei, People’s Republic of China
共同第一作者：
通讯作者：
通讯机构： [1]Cancer Research Institute, The Affiliated Hospital of Guilin Medical University, Guilin 541001 Guangxi, People’s Republic of China [2]Guangxi Health Commission Key Laboratory of Novel Onco-Kinases in Target Therapy, The Affiliated Hospital of Guilin Medical University, 541001 Guilin, Guangxi, People’s Republic of China [3]Department of Biochemistry and Molecular Biology, School of Basic Medicine, Huazhong University of Science and Technology, 430030 Wuhan, Hubei, People’s Republic of China [9]Department of Thoracic Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, 510080Guangzhou, People’s Republic of China [10]The Second School of Clinical Medicine, Southern Medical University, 510515 Guangzhou, People’s Republic of China [12]Guangxi Key Laboratory of Molecular Medicine in Liver Injury and Repair, the Affiliated Hospital of Guilin Medical University, 541001 Guilin, Guangxi, People’sRepublic of China
推荐引用方式(GB/T 7714)：
Xiao Juanjuan,Zhang Lu,Yi Huijun,et al.Inhibiting ALK-TOPK signaling pathway promotes cell apoptosis of ALK-positive NSCLC[J].CELL DEATH & DISEASE.2022,13(9):doi:10.1038/s41419-022-05260-3.
APA：
Xiao Juanjuan,Zhang Lu,Yi Huijun,Zou Ling,Mo Jianmei...&Zhu Feng.(2022).Inhibiting ALK-TOPK signaling pathway promotes cell apoptosis of ALK-positive NSCLC.CELL DEATH & DISEASE,13,(9)
MLA：
Xiao Juanjuan,et al."Inhibiting ALK-TOPK signaling pathway promotes cell apoptosis of ALK-positive NSCLC".CELL DEATH & DISEASE 13..9(2022)

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