CacyBP/SIP promotes the proliferation of colon cancer cells

被引：19

作者：

Zhai, Huihong ^{[1
,2
]}

Shi, Yongquan ^{[1
]}

Chen, Xiong ^{[1
]}

Wang, Jun ^{[1
]}

Lu, Yuanyuan ^{[1
]}

Zhang, Faming ^{[1
]}

Liu, Zhengxiong ^{[1
]}

Lei, Ting ^{[1
]}

Fan, Daiming ^{[1
]}

机构：

[1] Fourth Mil Med Univ, Xijing Hosp, Inst Digest Dis, State Key Lab Canc Biol, Xian, Peoples R China

[2] Capital Med Univ, Beijing Friendship Hosp, Dept Gastroenterol, Natl Clin Res Ctr Digest Dis, Beijing, Peoples R China

来源：

PLOS ONE | 2017年 / 12卷 / 02期

基金：

中国国家自然科学基金;

关键词：

CALCYCLIN-BINDING-PROTEIN; TUMOR PROMOTER; GASTRIN; TRANSLOCATION; DEGRADATION; PROTEOLYSIS; P27(KIP1); PATHWAY; GROWTH; MECHANISMS;

D O I：

10.1371/journal.pone.0169959

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

CacyBP/SIP is a component of the ubiquitin pathway and is overexpressed in several transformed tumor tissues, including colon cancer, which is one of the most common cancers worldwide. It is unknown whether CacyBP/SIP promotes the proliferation of colon cancer cells. This study examined the expression level, subcellular localization, and binding activity of CacyBP/SIP in human colon cancer cells in the presence and absence of the hormone gastrin. We found that CacyBP/SIP was expressed in a high percentage of colon cancer cells, but not in normal colonic surface epithelium. CacyBP/SIP promoted the cell proliferation of colon cancer cells under both basal and gastrin stimulated conditions as shown by knockdown studies. Gastrin stimulation triggered the translocation of CacyBP/SIP to the nucleus, and enhanced interaction between CacyBP/SIP and SKP1, a key component of ubiquitination pathway which further mediated the proteasome-dependent degradation of p27(kip1) protein. The gastrin induced reduction in p27(kip1) was prevented when cells were treated with the proteasome inhibitor MG132. These results suggest that CacyBP/SIP may be promoting growth of colon cancer cells by enhancing ubiquitin-mediated degradation of p27(kip1).

引用

页数：16

共 40 条

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