Evidence map›Paper›PMID 42098139›Full record

ArticleNature communications2026

GLUT6-facilitated noncanonical glucose metabolic rewiring enables resistance to targeted cancer therapy.

Huimin Lei, Ruixue Xia, Yabin Tang, Jun Lu, Chan Xiang, Yujing Li, Hongyu Liu, Peichen Zou, Ayinazhaer Aihemaiti, Wei Zhang and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

16 authors.

Huimin Lei *Department of Pharmacology and Chemical Biology, College of Basic Medical Sciences, Shanghai Jiao Tong University School of Medicine, Collaborative Innovation Center for Clinical and Translational Science by Chinese Ministry of Education & Shanghai, Shanghai, China.
Ruixue Xia *Department of Pharmacology and Chemical Biology, College of Basic Medical Sciences, Shanghai Jiao Tong University School of Medicine, Collaborative Innovation Center for Clinical and Translational Science by Chinese Ministry of Education & Shanghai, Shanghai, China.
Yabin Tang *Department of Pharmacology and Chemical Biology, College of Basic Medical Sciences, Shanghai Jiao Tong University School of Medicine, Collaborative Innovation Center for Clinical and Translational Science by Chinese Ministry of Education & Shanghai, Shanghai, China.
Jun Lu *Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.ORCID http://orcid.org/0000-0002-7343-9706
Chan XiangDepartment of Pathology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Yujing LiDepartment of Respiratory and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Hongyu LiuDepartment of Respiratory and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Peichen ZouDepartment of Pharmacology and Chemical Biology, College of Basic Medical Sciences, Shanghai Jiao Tong University School of Medicine, Collaborative Innovation Center for Clinical and Translational Science by Chinese Ministry of Education & Shanghai, Shanghai, China.
Ayinazhaer AihemaitiDepartment of Pharmacology and Chemical Biology, College of Basic Medical Sciences, Shanghai Jiao Tong University School of Medicine, Collaborative Innovation Center for Clinical and Translational Science by Chinese Ministry of Education & Shanghai, Shanghai, China.
Wei ZhangDepartment of Respiratory and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Ying ShenDepartment of Pharmacology and Chemical Biology, College of Basic Medical Sciences, Shanghai Jiao Tong University School of Medicine, Collaborative Innovation Center for Clinical and Translational Science by Chinese Ministry of Education & Shanghai, Shanghai, China.ORCID http://orcid.org/0000-0003-0656-7377
Baohui HanDepartment of Respiratory and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.ORCID http://orcid.org/0000-0002-3950-3030
Yuchen HanDepartment of Pathology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.ORCID http://orcid.org/0000-0002-7942-5540
Hua ZhongDepartment of Respiratory and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. eddiedong8@hotmail.com.ORCID http://orcid.org/0000-0003-3097-5717
Hongzhuan ChenShuguang Lab of Future Health, Shanghai Frontiers Science Center of TCM Chemical Biology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China. yaoli@shsmu.edu.cn.ORCID http://orcid.org/0000-0002-5367-2949
Liang ZhuDepartment of Pharmacology and Chemical Biology, College of Basic Medical Sciences, Shanghai Jiao Tong University School of Medicine, Collaborative Innovation Center for Clinical and Translational Science by Chinese Ministry of Education & Shanghai, Shanghai, China. jyzhul@shsmu.edu.cn.ORCID http://orcid.org/0000-0002-9383-392X

Funding

National Natural Science Foundation of China (National Science Foundation of China) 82273950, 82003772, 82103050, 82372669, 82072573, 82272913Science and Technology Commission of Shanghai Municipality (Shanghai Municipal Science and Technology Commission) 21ZR1436700
6 · The paper itself

Abstract

Targeting glucose metabolism has long been pursued as an anticancer strategy, yet its clinical translation remains challenging. Achieving therapeutic selectivity requires identifying actionable metabolic distinctions between different malignant traits. Here, we uncover a noncanonical, lactate-independent glucose metabolic pathway facilitated by the glucose transporter 6 (GLUT6), which confers targeted therapy resistance in lung cancer. Downstream, GLUT6 promotes glucose influx and diversion toward methylglyoxal production, leading to kelch-like ECH-associated protein 1 (KEAP1) dimerization and nuclear factor erythroid 2-related factor 2 (NRF2) pathway activation, driving resistance. Upstream, GLUT6 expression is transcriptionally upregulated by therapy-induced MYC associated zinc finger protein (MAZ) activation. Targeting GLUT6 prevents and overcomes EGFR and KRAS inhibitors resistance. Moreover, the MAZ-GLUT6-NRF2 axis correlates with clinical treatment response and relapse. The preferential reliance on GLUT6-a noncanonical transporter with minimal systemic homeostasis perturbation-highlights its promise as a target for overcoming resistance and revitalizing glucose metabolism-based anticancer strategies.

Indexed as

Drug Resistance, NeoplasmGlucoseGlucose Transport Proteins, FacilitativeLung NeoplasmsAnimalsAntineoplastic AgentsCell Line, TumorDNA-Binding ProteinsErbB ReceptorsGene Expression Regulation, NeoplasticHumansMetabolic ReprogrammingMiceNF-E2-Related Factor 2Proto-Oncogene Proteins p21(ras)PyruvaldehydeAntineoplastic AgentsDNA-Binding ProteinsErbB ReceptorsGlucoseGlucose Transport Proteins, FacilitativeNF-E2-Related Factor 2Proto-Oncogene Proteins p21(ras)PyruvaldehydeTranscription Factors

Identifiers

PMID42098139
PMCPMC13365234

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.