Evidence mapPaperPMID 41744824Full record

ArticleCells2026

WBP2 Attenuates Metformin Response in HER2-Positive Breast Cancer Cells by Repressing AMPK Activation and Inducing a Lower AMP:ATP Ratio State Through Enhanced ATP Production.

Hexian Lin, Shin-Ae Kang, Fei Xie, Yvonne Xinyi Lim, Sock Hong Seah, Amir Sabbaghian, Ssu-Yi Lu, Ting Gang Chew, Lih-Wen Deng, Shu Wang and 2 more

Abstract read
In one paragraph

Article in Cells, 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

12 authors.

Hexian LinSchool of Medicine, Zhejiang University-University of Edinburgh Institute, Zhejiang University, Hangzhou 314400, China.ORCID 0000-0002-1570-0291
Shin-Ae KangDepartment of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore.
Fei XieDepartment of Breast Disease Center, Peking University People's Hospital, Beijing 100044, China.
Yvonne Xinyi LimIntegrative Sciences and Engineering Programme, National University of Singapore, Singapore 119077, Singapore.ORCID 0000-0002-8070-2779
Sock Hong SeahDepartment of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore.ORCID 0000-0001-5453-8672
Amir SabbaghianSchool of Medicine, Zhejiang University-University of Edinburgh Institute, Zhejiang University, Hangzhou 314400, China.ORCID 0000-0003-0141-3547
Ssu-Yi LuDepartment of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore.
Ting Gang ChewSchool of Medicine, Zhejiang University-University of Edinburgh Institute, Zhejiang University, Hangzhou 314400, China.
Lih-Wen DengIntegrative Sciences and Engineering Programme, National University of Singapore, Singapore 119077, Singapore.ORCID 0000-0002-4985-7844
Shu WangDepartment of Breast Disease Center, Peking University People's Hospital, Beijing 100044, China.ORCID 0000-0002-8651-4795
E-Shyong TaiDepartment of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore.ORCID 0000-0003-2929-8966
Yoon Pin LimDepartment of Cancer Biology & Innovation, Guoke Ningbo Life Science and Health Industry Research Institute, Ningbo 315000, China.ORCID 0000-0002-0090-7556

Funding

National level talent program grant awarded by the Ministry of Education, China 2023RC002National Medical Research Council NMRC/OFIRG/0034/2017
6 · The paper itself

Abstract

Metformin is an antidiabetic drug that has been tested widely as an anti-cancer agent. However, data from clinical trials have been mixed. Evidence for metformin's efficacy in HER2+ breast cancer exists. Hence, we evaluated whether WBP2, a HER2-coamplified gene, can regulate the response of HER2+ breast cancer to metformin. Identification of biomarkers for predicting metformin response has implications in repurposing metformin for precision oncology. The effect of WBP2 on breast cancer response to metformin was studied using in vitro and mouse models. The mechanism of WBP2 on metformin-induced AMPK activation was elucidated, and its co-expression with p-AMPK was examined in clinical specimens using IHC. RNA-seq analyses were performed to elucidate WBP2's mechanism in energy metabolism. WBP2 inhibited the metformin response of HER2+ breast cancer in vitro and in vivo. These effects were concomitant with WBP2-mediated repression of metformin-induced AMPK activation and mTOR inhibition in HER2+ breast cancer cells, a lower AMP:ATP ratio state, and enhanced glycolytic capacity and mitochondria respiration. Analysis of HER2-positive breast cancer samples supports the negative correlation between WBP2 expression and activated AMPK observed in vitro. RNA-seq analysis revealed the potential mechanism of WBP2 in regulating ATP production processes and preferential effect of WBP2 on metformin response in HER2+ breast cancer. This study reported a novel role of WBP2 in cancer metabolism and energetics that contributes new insights into the molecular etiology of cancer. WBP2 may be a biomarker for patient stratification, paving the way towards repurposing metformin for precision oncology.

Indexed as

biomarkerdrug repurposingHER2-positive breast cancermetforminWW-domain binding protein 2

Identifiers

PMID41744824
PMCPMC12939031

What Socratic 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 Socratic graph.