Evidence map›Paper›PMID 28534518›Full record

ArticleOncogene2017

CDK20 interacts with KEAP1 to activate NRF2 and promotes radiochemoresistance in lung cancer cells.

Q Wang, J Ma, Y Lu, S Zhang, J Huang, J Chen, J-X Bei, K Yang, G Wu, K Huang and 2 more

Abstract read
PubMed Publisher
In one paragraph

Article in Oncogene, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed
3.7field-weighted citation impact, top 6% 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

57 citing papers in PubMed, 81 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

12 authors at 3 institutions in 2 countries.

Q WangCancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
J MaCancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Y LuCancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
S ZhangCancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
J HuangCancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
J ChenCancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
J-X BeiDepartment of Experimental Research, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China.
K YangCancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
G WuCancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
K HuangClinic Center of Human Gene Research, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
J ChenDepartment of Experimental Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
S XuCancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Union Hospital · CNHuazhong University of Science and Technology · CNSun Yat-sen University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Radiochemoresistance is considered the main cause of local recurrence and distant metastasis in lung cancer. However, the underlying mechanisms of radiochemoresistance remain to be uncovered. In this study, we determine the functions of cell cycle-related kinase (CDK20) in radiochemoresistance. CDK20 is a newly identified protein kinase, which plays critical roles in cell growth and proliferation in several types of cancer. Using tandem affinity purification technology, we provide evidences that CDK20 binds to the ubiquitin ligase Kelch-like ECH-associated protein 1 (KEAP1), which targets transcriptional factor nuclear factor erythroid-2-related factor 2 (NRF2) for degradation. We show that this interaction is mediated by an evolutionarily conserved ETGE motif on CDK20. Furthermore, we demonstrate that CDK20 competes with NRF2 for KEAP1 binding, enhances the transcriptional activity of NRF2 and lowers the cellular reactive oxygen species level. Moreover, CDK20-depleted cells display impaired cell proliferation, defective G2/M arrest and increased radiochemosensitivity in lung cancer. These phenotypes induced by CDK20 knockdown are partially dependent on NRF2 inactivation. More importantly, CDK20 is overexpressed in human lung cancer tissues, as determined by immunostaining. Collectively, our results suggest that CDK20 positively modulate the KEAP1-NRF2 cytoprotective pathway to regulate tumor progression and radiochemoresistance, implying that CDK20 is a novel, promising therapeutic target for lung cancer.

Indexed as

A549 CellsCell Line, TumorCell ProliferationChemoradiotherapyCyclin-Dependent KinasesDrug Resistance, NeoplasmHumansKelch-Like ECH-Associated Protein 1Lung NeoplasmsNF-E2-Related Factor 2Radiation ToleranceCyclin-Dependent KinasesKEAP1 protein, humanKelch-Like ECH-Associated Protein 1NFE2L2 protein, humanNF-E2-Related Factor 2

Identifiers

PMID28534518
OpenAlexW2620498868

What OpenQuestion holds

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Registered trials

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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.