Inhibition of never in mitosis A (NIMA)-related kinase-4 reduces survivin expression and sensitizes cancer cells to TRAIL-induced cell death

被引：14

作者：

Park, So Jung ^{[1
]}

Jo, Doo Sin ^{[1
]}

Jo, Se-Young ^{[2
]}

Shin, Dong Woon ^{[1
]}

Shim, Sangmi ^{[3
]}

Jo, Yoon Kyung ^{[1
]}

Shin, Ji Hyun ^{[1
]}

Ha, Ye Jin ^{[2
]}

Jeong, Seong-Yun ^{[2
]}

Hwang, Jung Jin ^{[2
]}

Kim, Young Sam ^{[4
]}

Suh, Young-Ah ^{[2
]}

Chang, Jong Wook ^{[5
,6
]}

Kim, Jin Cheon ^{[2
,7
]}

Cho, Dong-Hyung ^{[1
]}

机构：

[1] Kyung Hee Univ, Grad Sch East West Med Sci, Gyeonggi Do 17104, South Korea

[2] Univ Ulsan, Coll Med, Asan Med Ctr, Asan Inst Med Res, Seoul 05505, South Korea

[3] Seoul Natl Univ, Coll Med, Dept Biomed Sci, Seoul 03080, South Korea

[4] Yonsei Univ, Coll Med, Dept Internal Med, Seoul 03722, South Korea

[5] Samsung Med Ctr, Res Inst Future Med, Stem Cell & Regenerat Med Inst, Seoul 06351, South Korea

[6] Sungkyunkwan Univ, SAIHST, Dept Hlth Sci & Technol, Seoul 06351, South Korea

[7] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Surg, Seoul 05505, South Korea

来源：

ONCOTARGET | 2016年 / 7卷 / 40期

基金：

新加坡国家研究基金会;

关键词：

NEK4; survivin; cancer; TRAIL; APOPTOSIS; QUERCETIN; RESISTANCE; AUTOPHAGY; NECROPTOSIS; PROGRESSION; COMPLEXITY; PATHWAYS; FAMILY;

D O I：

10.18632/oncotarget.11781

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The tumor necrosis factor-related apoptosis inducing ligand (TRAIL) preferentially induces apoptosis in cancer cells. However, many tumors are resistant to TRAIL-induced apoptosis, and resistance mechanisms are not fully understood. To identify novel regulatory molecules of TRAIL resistance, we screened a siRNA library targeting the human kinome, and NEK4 (NIMA-related kinase-4) was identified. Knockdown of NEK4 sensitized TRAIL-resistant cancer cells and in vivo xenografts to cell death. In contrast, over expression of NEK4 suppressed TRAIL-induced cell death in TRAIL-sensitive cancer cells. In addition, loss of NEK4 resulted in decrease of the antiapoptotic protein survivin, but an increase in apoptotic cell death. Interestingly, NEK4 was highly upregulated in tumor tissues derived from patients with lung cancer and colon cancer. These results suggest that inhibition of NEK4 sensitizes cancer cells to TRAIL-induced apoptosis by regulation of survivin expression.

引用

页码：65957 / 65967

页数：11

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