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CacyBP/SIP promotes the proliferation of colon cancer cells.
- Source :
-
PloS one [PLoS One] 2017 Feb 14; Vol. 12 (2), pp. e0169959. Date of Electronic Publication: 2017 Feb 14 (Print Publication: 2017). - Publication Year :
- 2017
-
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.<br />Competing Interests: The authors have declared that no competing interests exist.
- Subjects :
- Active Transport, Cell Nucleus genetics
Calcium-Binding Proteins genetics
Cell Line, Tumor
Cell Nucleus genetics
Cell Nucleus pathology
Colonic Neoplasms genetics
Colonic Neoplasms pathology
Cyclin-Dependent Kinase Inhibitor p27 genetics
Cyclin-Dependent Kinase Inhibitor p27 metabolism
Female
Humans
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
Calcium-Binding Proteins biosynthesis
Cell Nucleus metabolism
Cell Proliferation
Colonic Neoplasms metabolism
Gene Expression Regulation, Neoplastic
Intestinal Mucosa metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 12
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 28196083
- Full Text :
- https://doi.org/10.1371/journal.pone.0169959