Please use this identifier to cite or link to this item: https://doi.org/10.3390/cancers13122873
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dc.titleA novel signature of ccnf-associated e3 ligases collaborate and counter each other in breast cancer
dc.contributor.authorChang, SC
dc.contributor.authorHung, CS
dc.contributor.authorZhang, BX
dc.contributor.authorHsieh, TH
dc.contributor.authorHsu, W
dc.contributor.authorDing, JL
dc.date.accessioned2021-07-06T10:55:17Z
dc.date.available2021-07-06T10:55:17Z
dc.date.issued2021-06-02
dc.identifier.citationChang, SC, Hung, CS, Zhang, BX, Hsieh, TH, Hsu, W, Ding, JL (2021-06-02). A novel signature of ccnf-associated e3 ligases collaborate and counter each other in breast cancer. Cancers 13 (12) : 2873-2873. ScholarBank@NUS Repository. https://doi.org/10.3390/cancers13122873
dc.identifier.issn20726694
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/193721
dc.description.abstractBreast cancer (BRCA) malignancy causes major fatalities amongst women worldwide. SCF (Skp1-cullin-F-box proteins) E3 ubiquitin ligases are the most well-known members of the ubiq-uitination–proteasome system (UPS), which promotes cancer initiation and progression. Recently, we demonstrated that FBXL8, a novel F-box protein (SCFF-boxes) of SCF E3 ligase, accelerates BRCA advancement and metastasis. Since SCFF-boxes is a key component of E3 ligases, we hypothesized that other SCFF-boxes besides FBXL8 probably collaborate in regulating breast carcinogenesis. In this study, we retrospectively profiled the transcriptome of BRCA tissues and found a notable upregu-lation of four SCFF-box E3 ligases (FBXL8, FBXO43, FBXO15, and CCNF) in the carcinoma tissues. Similar to FBXL8, the knockdown of FBXO43 reduced cancer cell viability and proliferation, sug-gesting its pro-tumorigenic role. The overexpression of CCNF inhibited cancer cell progression, in-dicating its anti-tumorigenic role. Unexpectedly, CCNF protein was markedly downregulated in BRCA tissues, although its mRNA level was high. We showed that both E3 ligases, FBXL8 and FZR1, pulled down CCNF. Double knockdown of FBXL8 and FZR1 caused CCNF accumulation. On the other hand, CCNF itself pulled down a tumorigenic factor, RRM2, and CCNF overexpres-sion reduced RRM2. Altogether, we propose a signature network of E3 ligases that collaboratively modulates CCNF anti-cancer activity. There is potential to target BRCA through modulation of the partnership axes of (i) CCNF-FBXL8, (ii) CCNF-FZR1, and (iii) CCNF-RRM2, particularly, via CCNF overexpression and activation and FBXL8/FZR1 suppression.
dc.publisherMDPI AG
dc.sourceElements
dc.subjectCCNF
dc.subjectE3 ubiquitin ligase
dc.subjectFBXL8
dc.subjectFZR1
dc.subjectRRM2
dc.subjectbreast cancer
dc.subjectmetastasis
dc.typeArticle
dc.date.updated2021-07-06T07:34:25Z
dc.contributor.departmentDEPT OF BIOLOGICAL SCIENCES
dc.description.doi10.3390/cancers13122873
dc.description.sourcetitleCancers
dc.description.volume13
dc.description.issue12
dc.description.page2873-2873
dc.published.statePublished
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