Evidence map›Paper›PMID 31112866›Full record

ArticleRedox biology2019

HSP60 silencing promotes Warburg-like phenotypes and switches the mitochondrial function from ATP production to biosynthesis in ccRCC cells.

Ruifang Teng, Zongyuan Liu, Haiping Tang, Wenhao Zhang, Yuling Chen, Renhua Xu, Liang Chen, Jiangping Song, Xiaohui Liu, Haiteng Deng

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Redox biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
2.7field-weighted citation impact, top 9% 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

45 citing papers in PubMed, 87 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

10 authors at 4 institutions in 2 countries.

Ruifang TengMOE Key Laboratory of Bioinformatics, Center for Synthetic and Systematic Biology, School of Life Sciences, Tsinghua University, Beijing, PR China.
Zongyuan LiuMOE Key Laboratory of Bioinformatics, Center for Synthetic and Systematic Biology, School of Life Sciences, Tsinghua University, Beijing, PR China.
Haiping TangMOE Key Laboratory of Bioinformatics, Center for Synthetic and Systematic Biology, School of Life Sciences, Tsinghua University, Beijing, PR China; Physical and Theoretical Chemistry Laboratory, University of Oxford, OX1 3QZ, Oxford, United Kingdom.
Wenhao ZhangMOE Key Laboratory of Bioinformatics, Center for Synthetic and Systematic Biology, School of Life Sciences, Tsinghua University, Beijing, PR China.
Yuling ChenMOE Key Laboratory of Bioinformatics, Center for Synthetic and Systematic Biology, School of Life Sciences, Tsinghua University, Beijing, PR China.
Renhua XuSchool of Nursing, Binzhou Medical University, Yantai, 264003, PR China.
Liang ChenState Key Laboratory of Cardiovascular Disease, Fuwai Hospital, Beijing, 100037, PR China.
Jiangping SongState Key Laboratory of Cardiovascular Disease, Fuwai Hospital, Beijing, 100037, PR China. Electronic address: fwsongjiangping@126.com.
Xiaohui LiuMOE Key Laboratory of Bioinformatics, Center for Synthetic and Systematic Biology, School of Life Sciences, Tsinghua University, Beijing, PR China. Electronic address: xiaohuiliu@biomed.tsinghua.edu.cn.
Haiteng DengMOE Key Laboratory of Bioinformatics, Center for Synthetic and Systematic Biology, School of Life Sciences, Tsinghua University, Beijing, PR China. Electronic address: dht@mail.tsinghua.edu.cn.
Tsinghua University · CNChinese Academy of Medical Sciences & Peking Union Medical College · CNBinzhou Medical University · CNUniversity of Oxford · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

HSP60 is a major mitochondrial chaperone for maintaining mitochondrial proteostasis. Our previous studies showed that HSP60 was significantly downregulated in clear cell renal cell carcinoma (ccRCC), the most common type of kidney cancer characterized by the classic Warburg effect. Here, we analyzed datasets in The Cancer Genome Atlas and revealed that higher HSP60 expression correlated with better overall survival in ccRCC patients. We also stably knocked down or overexpressed HSP60 in ccRCC cells to investigate the effects of HSP60 expression on the transition between oxidative phosphorylation and glycolysis. We confirmed that HSP60 knockdown increased cell proliferation, whereas its overexpression decreased cell growth. Proteomics and metabolomics revealed that HSP60 knockdown promoted Warburg-like phenotypes with enhanced glycolysis and decreased mitochondrial activity. Consistent with this finding, isotope tracing showed that the metabolic flow from glycolysis to TCA was reduced. However, HSP60 silencing enhanced mitochondrial functions in glutamine-directed biosynthesis with increased flow in two parts of the TCA cycle: Gln→αKG→OAA→Asp and Gln→αKG→ISO→acetyl-CoA, resulting in elevated de novo nucleotide synthesis and lipid synthesis. Proteomic analysis indicated that HSP60 silencing activated NRF2-mediated oxidative stress responses, while glutamate generated from glutamine increased glutathione synthesis for quenching excessive reactive oxygen species (ROS) produced upon elevated cell growth. We further found that HSP60 silencing activated the MEK/ERK/c-Myc axis to promote glutamine addiction, and confirmed that ccRCC cells were susceptible to oxidative stress and glutaminase inhibition. Collectively, our data show that HSP60 knockdown drives metabolic reprogramming in ccRCC to promote tumor progression and enhances mitochondrial-dependent biosynthesis.

Indexed as

Energy MetabolismGene SilencingAdenosine TriphosphateBiomarkersCarcinoma, Renal CellCell Line, TumorChaperonin 60Chromatography, LiquidGene ExpressionGene Knockdown TechniquesGlycolysisHumansKidney NeoplasmsMetabolomicsMitochondriaMitochondrial ProteinsAdenosine TriphosphateBiomarkersChaperonin 60HSPD1 protein, humanMitochondrial ProteinsReactive Oxygen SpeciesccRCCGlutamine metabolismHSP60Metabolic reprogramming

Identifiers

PMID31112866
PMCPMC6526248
OpenAlexW2946215758

What OpenQuestion holds

Textmetadata
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.