Evidence map›Paper›PMID 31262713›Full record

ArticleEBioMedicine2019

FAM129B, an antioxidative protein, reduces chemosensitivity by competing with Nrf2 for Keap1 binding.

Kai-Chun Cheng, Ruey-Jen Lin, Jing-Yan Cheng, Sheng-Hung Wang, Jyh-Cherng Yu, Jen-Chine Wu, Yuh-Jin Liang, Huan-Ming Hsu, John Yu, Alice L Yu

Open access · goldAbstract read
In one paragraph

Article in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed, 1 pooled it
2.2field-weighted citation impact, top 11% 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

30 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.

  1. Pooled it
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  18. The roles of KLHL family members in human cancers.American journal of cancer research · 2022
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  20. The intricacies of NRF2 regulation in cancer.Seminars in cancer biology · 2021
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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

10 authors at 4 institutions in 2 countries.

Kai-Chun ChengInstitute of Stem Cell & Translational Cancer Research, Chang Gung Memorial Hospital at Linkou, Chang Gung University, Taoyuan, Taiwan; Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan.
Ruey-Jen LinInstitute of Stem Cell & Translational Cancer Research, Chang Gung Memorial Hospital at Linkou, Chang Gung University, Taoyuan, Taiwan.
Jing-Yan ChengInstitute of Stem Cell & Translational Cancer Research, Chang Gung Memorial Hospital at Linkou, Chang Gung University, Taoyuan, Taiwan.
Sheng-Hung WangInstitute of Stem Cell & Translational Cancer Research, Chang Gung Memorial Hospital at Linkou, Chang Gung University, Taoyuan, Taiwan.
Jyh-Cherng YuGeneral Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
Jen-Chine WuInstitute of Stem Cell & Translational Cancer Research, Chang Gung Memorial Hospital at Linkou, Chang Gung University, Taoyuan, Taiwan.
Yuh-Jin LiangTranslational Research Division, Medical Research Department, Taipei Veterans General Hospital, Taipei, Taiwan.
Huan-Ming HsuGeneral Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
John YuInstitute of Stem Cell & Translational Cancer Research, Chang Gung Memorial Hospital at Linkou, Chang Gung University, Taoyuan, Taiwan.
Alice L YuInstitute of Stem Cell & Translational Cancer Research, Chang Gung Memorial Hospital at Linkou, Chang Gung University, Taoyuan, Taiwan; Department of Pediatrics, University of California in San Diego, San Diego, CA, USA. Electronic address: a1yu@ucsd.edu.
Chang Gung University · TWTri-Service General Hospital · TWNational Yang Ming Chiao Tung University · TWTaipei Veterans General Hospital · TW

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe transcription factor Nrf2 is a master regulator of antioxidant response. While Nrf2 activation may counter increasing oxidative stress in aging, its activation in cancer can promote cancer progression and metastasis, and confer resistance to chemotherapy and radiotherapy. Thus, Nrf2 has been considered as a key pharmacological target. Unfortunately, there are no specific Nrf2 inhibitors for therapeutic application. Moreover, high Nrf2 activity in many tumors without Keap1 or Nrf2 mutations suggests that alternative mechanisms of Nrf2 regulation exist.

methodsInteraction of FAM129B with Keap1 is demonstrated by immunofluorescence, colocalization, co-immunoprecipitation and mammalian two-hybrid assay. Antioxidative function of FAM129B is analyzed by measuring ROS levels with DCF/flow cytometry, Nrf2 activation using luciferase reporter assay and determination of downstream gene expression by qPCR and wester blotting. Impact of FAM129B on in vivo chemosensitivity is examined in mice bearing breast and colon cancer xenografts. The clinical relevance of FAM129B is assessed by qPCR in breast cancer samples and data mining of publicly available databases.

findingsWe have demonstrated that FAM129B in cancer promotes Nrf2 activity by reducing its ubiquitination through competition with Nrf2 for Keap1 binding via its DLG and ETGE motifs. In addition, FAM129B reduces chemosensitivity by augmenting Nrf2 antioxidative signaling and confers poor prognosis in breast and lung cancer.

interpretationThese findings demonstrate the important role of FAM129B in Nrf2 activation and antioxidative response, and identify FMA129B as a potential therapeutic target. FUND: The Chang Gung Medical Foundation (Taiwan) and the Ministry of Science and Technology (Taiwan).

Indexed as

AgingAnimalsAntioxidantsBreast NeoplasmsColonic NeoplasmsDrug Resistance, NeoplasmFemaleGene Expression Regulation, NeoplasticHCT116 CellsHumansKelch-Like ECH-Associated Protein 1MiceNF-E2-Related Factor 2Oxidative StressPhosphoproteinsProtein BindingAntioxidantsKelch-Like ECH-Associated Protein 1NFE2L2 protein, humanNF-E2-Related Factor 2NIBAN2 protein, humanPhosphoproteinsAntioxidationChemosensitivityFAM129BKeap1Nrf2

Identifiers

PMID31262713
PMCPMC6642435
OpenAlexW2954002136

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.