The potassium channel KCa3.1 promotes cell proliferation by activating SKP2 and metastasis through the EMT pathway in hepatocellular carcinoma

被引：38

作者：

Du, Yehui ^{[1
,2
,3
,4
]}

Song, Wenfeng ^{[1
,2
,3
,4
]}

Chen, Jian ^{[1
,2
,3
,4
]}

Chen, Hao ^{[1
,2
,3
,4
]}

Xuan, Zefeng ^{[1
,2
,3
,4
]}

Zhao, Long ^{[1
,2
,3
,4
]}

Chen, Jun ^{[1
,2
,3
,4
]}

Jin, Cheng ^{[1
,2
,3
,4
]}

Zhou, Mengqiao ^{[1
,2
,3
,4
]}

Tuo, Biguang ^{[5
]}

Zhao, Yongchao ^{[1
,2
,6
]}

Zheng, Shusen ^{[1
,2
,3
,4
]}

Song, Penghong ^{[1
,2
,3
,4
]}

机构：

[1] Zhejiang Univ, Affiliated Hosp 1, Div Hepatobiliary & Pancreat Surg, Dept Surg,Sch Med, Hangzhou, Zhejiang, Peoples R China

[2] NHFPC Key Lab Combined Multiorgan Transplantat, Hangzhou, Zhejiang, Peoples R China

[3] Key Lab Organ Transplantat, Hangzhou, Zhejiang, Peoples R China

[4] Collaborat Innovat Ctr Diag Treatment Infect Dis, Hangzhou, Zhejiang, Peoples R China

[5] Zunyi Med Coll, Affiliated Hosp, Dept Gastroenterol, Zunyi, Peoples R China

[6] Zhejiang Univ, Sch Med, Inst Translat Med, Hangzhou, Zhejiang, Peoples R China

来源：

INTERNATIONAL JOURNAL OF CANCER | 2019年 / 145卷 / 02期

基金：

中国国家自然科学基金; 国家自然科学基金重大项目;

关键词：

KCa3.1; SKP2; RELN; hepatocellular carcinoma; BREAST-CANCER; POOR-PROGNOSIS; K+ CHANNELS; EXPRESSION; K(CA)3.1; P21(WAF1/CIP1); P27(KIP1); MIGRATION; REELIN; GROWTH;

D O I：

10.1002/ijc.32121

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The intermediate conductance calcium-activated potassium channel (KCa3.1) plays an important role in maintaining intracellular calcium homeostasis and is involved in the tumorigenesis of many human cancers. However, it is unknown whether KCa3.1 plays a role in the genesis of hepatocellular carcinoma (HCC), one of the most common malignant tumors worldwide with a very poor prognosis. In our study, we found that the expression of KCa3.1 was significantly elevated in poorly differentiated HCC tissues compared to adjacent noncancerous tissues. In vitro and in vivo experiments showed that KCa3.1 could promote cell proliferation, migration, and invasion of HCC. Mechanistically, KCa3.1 promoted cell cycle progression and migration and invasion of HCC cells by activating S-phase protein kinase 2 (SKP2) to trigger the degradation of p21 and p27 and targeting Reelin (RELN) to induce epithelial-mesenchymal transition (EMT), respectively. Taken together, our results demonstrate that KCa3.1 plays an important role in the genesis and progression of HCC, implying that it might be a promising therapeutic target in HCC.

引用

页码：503 / 516

页数：14

共 40 条

[21] Establishment of a hepatocellular carcinoma cell line with unique metastatic characteristics through in vivo selection and screening for metastasis-related genes through cDNA microarray [J].