CHIP/Stub1 functions as a tumor suppressor and represses NF-?B-mediated signaling in colorectal cancer
The carboxyl terminus of Hsc70-interacting protein (CHIP, also named Stub1), a U-box containing E3 ubiquitin ligase, is involved in degradation of certain oncogenic proteins. Recent studies indicated that CHIP suppresses tumor progression in human cancers by targeting Src-3, hypoxia inducible factor...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Journal Article |
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Oxford University Press
2014
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| Online Access: | http://hdl.handle.net/20.500.11937/28045 |
| _version_ | 1848752430338015232 |
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| author | Wang, Y. Ren, F. Wang, Y. Feng, Y. Wang, D. Jia, B. Qiu, Y. Wang, S. Yu, J. Sung, J. Xu, J. Zeps, Nikolajs Chang, Z. |
| author_facet | Wang, Y. Ren, F. Wang, Y. Feng, Y. Wang, D. Jia, B. Qiu, Y. Wang, S. Yu, J. Sung, J. Xu, J. Zeps, Nikolajs Chang, Z. |
| author_sort | Wang, Y. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | The carboxyl terminus of Hsc70-interacting protein (CHIP, also named Stub1), a U-box containing E3 ubiquitin ligase, is involved in degradation of certain oncogenic proteins. Recent studies indicated that CHIP suppresses tumor progression in human cancers by targeting Src-3, hypoxia inducible factor 1α, NF-κB, ErbB2 and c-Myc. Here, we report that CHIP was downregulated, predominantly, in the late stages of human colorectal cancer (CRC), and that the CHIP promoter was hypermethylated in CRC specimens. Overexpression of CHIP in HCT-116 cells resulted in impaired tumor growth in nude mice and decreased abilities of tumor cell migration and invasion. Conversely, depletion of CHIP in HCT-116 cells promoted tumor growth and increased tumor cell migration and invasion. CHIP was further found to negatively regulate NF-κB signaling in HCT-116 cells by promoting ubiquitination and degradation of p65, a subunit of the NF-κB complex. The suppressive effect of CHIP led to decreased expression of NF-κB-targeted oncogenes including Cyclin D1, c-Myc, MMP-2, VEGF and IL-8. We proposed that CHIP inhibits the malignancy of CRC cells, possibly through targeting NF-κB signaling. This study provides functional evidence for CHIP as a potential tumor suppressor in CRC, and CHIP expression may be a marker for stages of CRC. |
| first_indexed | 2025-11-14T08:08:30Z |
| format | Journal Article |
| id | curtin-20.500.11937-28045 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T08:08:30Z |
| publishDate | 2014 |
| publisher | Oxford University Press |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-280452017-09-13T15:14:32Z CHIP/Stub1 functions as a tumor suppressor and represses NF-?B-mediated signaling in colorectal cancer Wang, Y. Ren, F. Wang, Y. Feng, Y. Wang, D. Jia, B. Qiu, Y. Wang, S. Yu, J. Sung, J. Xu, J. Zeps, Nikolajs Chang, Z. The carboxyl terminus of Hsc70-interacting protein (CHIP, also named Stub1), a U-box containing E3 ubiquitin ligase, is involved in degradation of certain oncogenic proteins. Recent studies indicated that CHIP suppresses tumor progression in human cancers by targeting Src-3, hypoxia inducible factor 1α, NF-κB, ErbB2 and c-Myc. Here, we report that CHIP was downregulated, predominantly, in the late stages of human colorectal cancer (CRC), and that the CHIP promoter was hypermethylated in CRC specimens. Overexpression of CHIP in HCT-116 cells resulted in impaired tumor growth in nude mice and decreased abilities of tumor cell migration and invasion. Conversely, depletion of CHIP in HCT-116 cells promoted tumor growth and increased tumor cell migration and invasion. CHIP was further found to negatively regulate NF-κB signaling in HCT-116 cells by promoting ubiquitination and degradation of p65, a subunit of the NF-κB complex. The suppressive effect of CHIP led to decreased expression of NF-κB-targeted oncogenes including Cyclin D1, c-Myc, MMP-2, VEGF and IL-8. We proposed that CHIP inhibits the malignancy of CRC cells, possibly through targeting NF-κB signaling. This study provides functional evidence for CHIP as a potential tumor suppressor in CRC, and CHIP expression may be a marker for stages of CRC. 2014 Journal Article http://hdl.handle.net/20.500.11937/28045 10.1093/carcin/bgt393 Oxford University Press unknown |
| spellingShingle | Wang, Y. Ren, F. Wang, Y. Feng, Y. Wang, D. Jia, B. Qiu, Y. Wang, S. Yu, J. Sung, J. Xu, J. Zeps, Nikolajs Chang, Z. CHIP/Stub1 functions as a tumor suppressor and represses NF-?B-mediated signaling in colorectal cancer |
| title | CHIP/Stub1 functions as a tumor suppressor and represses NF-?B-mediated signaling in colorectal cancer |
| title_full | CHIP/Stub1 functions as a tumor suppressor and represses NF-?B-mediated signaling in colorectal cancer |
| title_fullStr | CHIP/Stub1 functions as a tumor suppressor and represses NF-?B-mediated signaling in colorectal cancer |
| title_full_unstemmed | CHIP/Stub1 functions as a tumor suppressor and represses NF-?B-mediated signaling in colorectal cancer |
| title_short | CHIP/Stub1 functions as a tumor suppressor and represses NF-?B-mediated signaling in colorectal cancer |
| title_sort | chip/stub1 functions as a tumor suppressor and represses nf-?b-mediated signaling in colorectal cancer |
| url | http://hdl.handle.net/20.500.11937/28045 |