Cited 5 times in
STAT3 Stabilizes IKKα Protein through Direct Interaction in Transformed and Cancerous Human Breast Epithelial Cells
DC Field | Value | Language |
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dc.contributor.author | 송나영 | - |
dc.date.accessioned | 2021-04-29T16:46:25Z | - |
dc.date.available | 2021-04-29T16:46:25Z | - |
dc.date.issued | 2021-01 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/182009 | - |
dc.description.abstract | Signal transducer and activator of transcription 3 (STAT3) and nuclear factor-κB (NF-κB) are two representative transcription factors that play a critical role in inflammation-associated tumorigenesis through multi-level cooperation. Unlike other types of tumors, breast carcinomas have shown a significant dependency on the non-classical NF-κB pathway as well as the classical one. The α subunit of the inhibitor of the κB kinase (IKK) complex, IKKα, is involved in both classical and non-classical activation of NF-κB. Although the cross-talk between STAT3 and NF-κB has been suggested in several studies, the interplay between STAT3 and the regulators of NF-κB including IKKα has not been fully clarified yet. In this study, we observed overexpression and co-localization of IKKα and STAT3 in human breast cancer tissues as well as in H-Ras transformed human breast epithelial (H-Ras MCF-10A) and breast cancer (MDA-MB-231) cells. By utilizing small interfering RNA (siRNA) technology, we were able to demonstrate that STAT3 up-regulated IKKα, but not IKKβ or IKKγ, in these cells. This was attributable to direct binding to and subsequent stabilization of IKKα protein by blocking the ubiquitin-proteasome system. Notably, we identified the lysine 44 residue of IKKα as a putative binding site for STAT3. Moreover, siRNA knockdown of IKKα attenuated viability, anchorage-independent growth and migratory capabilities of H-Ras MCF-10A cells. Taken together, these findings propose a novel mechanism responsible for NF-κB activation by STAT3 through stabilization of IKKα, which contributes to breast cancer promotion and progression. Thus, breaking the STAT3-IKKα alliance can be an alternative therapeutic strategy for the treatment of breast cancer. | - |
dc.description.statementOfResponsibility | open | - |
dc.language | English | - |
dc.publisher | MDPI | - |
dc.relation.isPartOf | CANCERS | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.title | STAT3 Stabilizes IKKα Protein through Direct Interaction in Transformed and Cancerous Human Breast Epithelial Cells | - |
dc.type | Article | - |
dc.contributor.college | College of Dentistry (치과대학) | - |
dc.contributor.department | Dept. of Oral Biology (구강생물학교실) | - |
dc.contributor.googleauthor | Young-Il Hahn | - |
dc.contributor.googleauthor | Soma Saeidi | - |
dc.contributor.googleauthor | Su-Jung Kim | - |
dc.contributor.googleauthor | Se-Young Park | - |
dc.contributor.googleauthor | Na-Young Song | - |
dc.contributor.googleauthor | Jie Zheng | - |
dc.contributor.googleauthor | Do-Hee Kim | - |
dc.contributor.googleauthor | Han-Byoel Lee | - |
dc.contributor.googleauthor | Wonshik Han | - |
dc.contributor.googleauthor | Dong-Young Noh | - |
dc.contributor.googleauthor | Hye-Kyung Na | - |
dc.contributor.googleauthor | Young-Joon Surh | - |
dc.identifier.doi | 10.3390/cancers13010082 | - |
dc.contributor.localId | A05713 | - |
dc.relation.journalcode | J03449 | - |
dc.identifier.eissn | 2072-6694 | - |
dc.identifier.pmid | 33396715 | - |
dc.subject.keyword | H-Ras MCF-10A cells | - |
dc.subject.keyword | IKKα | - |
dc.subject.keyword | STAT3 | - |
dc.subject.keyword | breast cancer | - |
dc.subject.keyword | non-canonical NF-κB pathway | - |
dc.contributor.alternativeName | Song, Na-Young | - |
dc.contributor.affiliatedAuthor | 송나영 | - |
dc.citation.volume | 13 | - |
dc.citation.number | 1 | - |
dc.citation.startPage | 82 | - |
dc.identifier.bibliographicCitation | CANCERS, Vol.13(1) : 82, 2021-01 | - |
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