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
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