Evidence map›Paper›PMID 32784654›Full record

ArticleCancers2020

Human FBXL8 Is a Novel E3 Ligase Which Promotes BRCA Metastasis by Stimulating Pro-Tumorigenic Cytokines and Inhibiting Tumor Suppressors.

Shu-Chun Chang, Wayne Hsu, Emily Chia-Yu Su, Chin-Sheng Hung, Jeak Ling Ding

Open access · goldAbstract read
In one paragraph

Article in Cancers, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 1 pooled it
1.8field-weighted citation impact, top 14% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 3 institutions in 2 countries.

Shu-Chun ChangThe Ph.D. Program for Translational Medicine, College for Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan.
Wayne HsuDivision of Acute Care Surgery, Department of Surgery, Taipei Medical University Hospital, Taipei 110, Taiwan.
Emily Chia-Yu SuGraduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan.ORCID 0000-0003-4801-5159
Chin-Sheng HungDivision of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, Taipei 110, Taiwan.ORCID 0000-0002-9515-2036
Jeak Ling DingDepartment of Biological Sciences, National University of Singapore, Singapore 117543, Singapore.ORCID 0000-0003-4578-370X
Taipei Medical University Hospital · TWNational University of Singapore · SGTaipei Medical University · TW

Funding

Ministry of Education - Singapore R-154-000-A76-114Ministry of Science and Technology, Taiwan MOST107-2314-B-038-066Ministry of Science and Technology, Taiwan MOST 109-2314-B-038-087National University of Singapore Graduate School of Integrative Sciences and Engineering C-154-000-017-091Taipei Medical University 105TMU-TMUH-06Taipei Medical University TMU104-AE1-B10
6 · The paper itself

Abstract

The initiation and progression of breast cancer (BRCA) is associated with inflammation and immune-overactivation, which is critically modulated by the E3 ubiquitin ligase. However, the underlying mechanisms and key factors involved in BRCA formation and disease advancement remains under-explored. By retrospective studies of BRCA patient tissues; and gene knockdown and gain/loss-of-function studies, we uncovered a novel E3 ligase, FBXL8, in BRCA. A signature expression profile of F-box factors that specifically target and degrade proteins involved in cell death/survival, was identified. FBXL8 emerged as a prominent member of the F-box factors. Ex vivo analysis of 1349 matched BRCA tissues indicated that FBXL8 promotes cell survival and tumorigenesis, and its level escalates with BRCA progression. Knockdown of FBXL8 caused: (i) intrinsic apoptosis, (ii) inhibition of cell migration and invasion, (iii) accumulation of two tumor-suppressors, CCND2 and IRF5, and (iv) downregulation of cancer-promoting cytokines/chemokines; all of which curtailed the tumor microenvironment and displayed potential to suppress cancer progression. Co-IP study suggests that two tumor-suppressors, CCND2 and IRF5 are part of the immune-complex of FBXL8. The protein levels of CCND2 and IRF5 inversely correlated with FBXL8 expression, implying that FBXL8 E3 ligase was associated with the degradation of CCND2 and IRF5. Altogether, we propose the exploitation of the ubiquitin signaling axis of FBXL8-CCND2-IRF5 for anti-cancer strategies and potential therapeutics.

Indexed as

breast cancer (BRCA) and metastasisCCND2FBXL8 SCF E3 ubiquitin ligaseIRF5pro-tumorigenic microenvironment

Identifiers

PMID32784654
PMCPMC7465060
OpenAlexW3047778215

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.