KCNN4 promotes the progression of lung adenocarcinoma by activating the AKT and ERK signaling pathways

被引:12
|
作者
Xu, Ping [1 ,2 ,3 ]
Mo, Xiao [1 ,2 ,3 ]
Xia, Ruixue [7 ]
Jiang, Long [8 ]
Zhang, Chengfei [1 ,2 ,3 ]
Xu, Haojun [1 ,2 ,3 ]
Sun, Qi [1 ,2 ,3 ,9 ]
Zhou, Guoren [4 ,5 ,6 ]
Zhang, Yijie [7 ]
Wang, Yongsheng [9 ]
Xia, Hongping [1 ,2 ,3 ,4 ,5 ,6 ,7 ]
机构
[1] Nanjing Med Univ, Sch Basic Med Sci, Dept Pathol, Nanjing 211166, Jiangsu, Peoples R China
[2] Nanjing Med Univ, Sir Run Run Hosp, Nanjing 211166, Jiangsu, Peoples R China
[3] Nanjing Med Univ, Key Lab Antibody Tech, Natl Hlth Commiss, Nanjing 211166, Jiangsu, Peoples R China
[4] Nanjing Med Univ, Jiangsu Canc Hosp, Nanjing 210009, Jiangsu, Peoples R China
[5] Nanjing Med Univ, Affiliated Canc Hosp, Nanjing 210009, Jiangsu, Peoples R China
[6] Nanjing Med Univ, Jiangsu Inst Canc Res, Nanjing 210009, Jiangsu, Peoples R China
[7] Henan Univ, Huaihe Hosp, Dept Resp & Crit Care Med, Kaifeng 475000, Henan, Peoples R China
[8] Shanghai Jiao Tong Univ, Shanghai Chest Hosp, Shanghai Lung Canc Ctr, Shanghai, Peoples R China
[9] Nanjing Univ, Med Sch, Nanjing Drum Tower Hosp, Nanjing 210008, Jiangsu, Peoples R China
关键词
KCNN4; lung adenocarcinoma; AKT; ERK; proliferation; CANCER CELLS; MACROPHAGES; INHIBITION; EXPRESSION; INCREASES; PROGNOSIS; APOPTOSIS; KCA3.1;
D O I
10.3233/CBM-201045
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
BACKGROUND: Potassium channels, encoded by more than seventy genes, are cell excitability transmembrane proteins and become evident to play essential roles in tumor biology. OBJECTIVE: The deregulation of potassium channel genes has been related to cancer development and patient prognosis. The objective of this study is to understand the role of potassium channels in lung cancer. METHODS: We examined all potassium channel genes and identified that KCNN4 is the most significantly overexpressed one in lung adenocarcinoma. The role and mechanism of KCNN4 in lung adenocarcinoma were further investigated by in vitro cell and molecular assay and in vivo mouse xenograft models. RESULTS: We revealed that the silencing of KCNN4 significantly inhibits cell proliferation, migration, invasion, and tumorigenicity of lung adenocarcinoma. Further studies showed that knockdown of KCNN4 promotes cell apoptosis, induces cell cycle arrested in the S phase, and is associated with the epithelial to mesenchymal transition (EMT) process. Most importantly, we demonstrated that KCNN4 regulates the progression of lung adenocarcinoma through P13K/AKT and MEK/ERK signaling pathways. The use of inhibitors that targeted AKT and ERK also significantly inhibit the proliferation and metastasis of lung adenocarcinoma cells. CONCLUSIONS: This study investigated the function and mechanism of KCNN4 in lung adenocarcinoma. On this basis, this means that KCNN4 can be used as a tumor marker for lung adenocarcinoma and is expected to become an important target for a potential drug.
引用
收藏
页码:187 / 201
页数:15
相关论文
共 50 条
  • [1] KCNN4 is a diagnostic and prognostic biomarker that promotes papillary thyroid cancer progression
    Wen, Jialiang
    Lin, Bangyi
    Lin, Lizhi
    Chen, Yizuo
    Wang, Ouchen
    [J]. AGING-US, 2020, 12 (16): : 16437 - 16456
  • [2] KCNN4 promotes invasion and metastasis through the MAPK/ERK pathway in hepatocellular carcinoma
    Li, Qiu-Ting
    Feng, Yi-Ming
    Ke, Zun-Hui
    Qiu, Meng-Jun
    He, Xiao-Xiao
    Wang, Meng-Meng
    Li, Ya-Nan
    Xu, Jing
    Shi, Liang-Liang
    Xiong, Zhi-Fan
    [J]. JOURNAL OF INVESTIGATIVE MEDICINE, 2020, 68 (01) : 68 - 74
  • [3] INTS6 promotes colorectal cancer progression by activating of AKT and ERK signaling
    Ding, Xufen
    Chen, Tianwei
    Shi, Qian
    Nan, Peng
    Wang, Xiang
    Xie, Dong
    Li, Jingjing
    [J]. EXPERIMENTAL CELL RESEARCH, 2021, 407 (02)
  • [4] ZNF251 promotes the progression of lung cancer by activating ERK signaling
    Zhong, Chenxi
    Chen, Chunji
    Yao, Feng
    Fang, Wentao
    [J]. CANCER SCIENCE, 2020, 111 (09) : 3236 - 3244
  • [5] LncRNA THOR promotes endometrial cancer progression through the AKT and ERK signaling pathways
    Zhang, Han-Qiu
    Li, Tao
    Li, Cheng
    Hu, Hong-Tao
    Zhu, Si-Meng
    Lu, Jia-Qi
    Chen, Xiao-Jun
    Huang, He-Feng
    Wu, Yan-Ting
    [J]. MEDICAL ONCOLOGY, 2022, 39 (12)
  • [6] LncRNA THOR promotes endometrial cancer progression through the AKT and ERK signaling pathways
    Han-Qiu Zhang
    Tao Li
    Cheng Li
    Hong-Tao Hu
    Si-Meng Zhu
    Jia-Qi Lu
    Xiao-Jun Chen
    He-Feng Huang
    Yan-Ting Wu
    [J]. Medical Oncology, 39
  • [7] Centromere protein N promotes lung adenocarcinoma progression by activating PI3K/AKT signaling pathway
    Zheng, Yi
    You, Hui
    Duan, Jingzhu
    Chen, Biyu
    Wu, Chenlin
    Chen, Peipei
    Wang, Meifang
    [J]. GENES & GENOMICS, 2022, 44 (09) : 1039 - 1049
  • [8] Centromere protein N promotes lung adenocarcinoma progression by activating PI3K/AKT signaling pathway
    Yi Zheng
    Hui You
    Jingzhu Duan
    Biyu Chen
    Chenlin Wu
    Peipei Chen
    Meifang Wang
    [J]. Genes & Genomics, 2022, 44 : 1039 - 1049
  • [9] MUC13 promotes lung cancer development and progression by activating ERK signaling
    Pang, Yao
    Zhang, Yu
    Zhang, Hong-Yi
    Wang, Wen-Hao
    Jin, Gang
    Liu, Jia-Wei
    Zhu, Zi-Jiang
    [J]. ONCOLOGY LETTERS, 2022, 23 (01)
  • [10] Long non-coding RNA CUDR promotes malignant phenotypes in pancreatic ductal adenocarcinoma via activating AKT and ERK signaling pathways
    Liang, Xing
    Qi, Meiyan
    Wu, Rui
    Liu, Anan
    Chen, Danlei
    Tang, Liang
    Chen, Jun
    Hu, Xiangui
    Li, Wei
    Zhan, Lixing
    Shao, Chenghao
    [J]. INTERNATIONAL JOURNAL OF ONCOLOGY, 2018, 53 (06) : 2671 - 2682