CacyBP/SIP promotes the proliferation of colon cancer cells

Huihong Zhai; Yongquan Shi; Xiong Chen; Jun Wang; Yuanyuan Lu; Faming Zhang; Zhengxiong Liu; Ting Lei; Daiming Fan

doi:10.1371/journal.pone.0169959

CacyBP/SIP promotes the proliferation of colon cancer cells

PLoS One. 2017 Feb 14;12(2):e0169959. doi: 10.1371/journal.pone.0169959. eCollection 2017.

Authors

Huihong Zhai¹, Yongquan Shi¹, Xiong Chen¹, Jun Wang¹, Yuanyuan Lu¹, Faming Zhang¹, Zhengxiong Liu¹, Ting Lei¹, Daiming Fan¹

Affiliation

¹ State Key Laboratory of Cancer Biology, Institute of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China.

Abstract

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 p27kip1 protein. The gastrin induced reduction in p27kip1 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 p27kip1.

MeSH terms

Active Transport, Cell Nucleus / genetics
Calcium-Binding Proteins / biosynthesis*
Calcium-Binding Proteins / genetics
Cell Line, Tumor
Cell Nucleus / genetics
Cell Nucleus / metabolism*
Cell Nucleus / pathology
Cell Proliferation*
Colonic Neoplasms / genetics
Colonic Neoplasms / metabolism*
Colonic Neoplasms / pathology
Cyclin-Dependent Kinase Inhibitor p27 / genetics
Cyclin-Dependent Kinase Inhibitor p27 / metabolism
Female
Gene Expression Regulation, Neoplastic*
Humans
Intestinal Mucosa / metabolism*
Intestinal Mucosa / pathology
Male
Proteasome Endopeptidase Complex / genetics
Proteasome Endopeptidase Complex / metabolism
Proteolysis
S-Phase Kinase-Associated Proteins / genetics
S-Phase Kinase-Associated Proteins / metabolism
Ubiquitination

Substances

CACYBP protein, human
CDKN1B protein, human
Calcium-Binding Proteins
S-Phase Kinase-Associated Proteins
SKP1 protein, human
Cyclin-Dependent Kinase Inhibitor p27
Proteasome Endopeptidase Complex

Grants and funding

This work was funded by the National Natural Science Foundation of China (No. 30860321), National Key Technologies R&D Program (No.2015BAI13B09), the Science Foundation of Ningxia (NZ0897) and the Research Fund of Ningxia Medical University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.