Evidence map›Paper›PMID 41997974›Full record

ArticleNature communications2026

ELMO2 is a therapeutic vulnerability in mesenchymal-like and drug-resistant non-small cell lung cancer.

Min Li, Ying Xue, Yuhan Chang, Fan Xu, Feizhen Wu, Xinjian Tian, Jie Hu, Yijun Song, Xufen Yu, Fei Zhou and 4 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

14 authors.

Min Li *Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China.ORCID http://orcid.org/0000-0002-0523-9171
Ying Xue *Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.
Yuhan Chang *Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China.
Fan Xu *Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China.ORCID http://orcid.org/0000-0002-8751-3364
Feizhen WuIntelligent Medicine Institute, Fudan University, Shanghai, China.ORCID http://orcid.org/0000-0002-1265-9887
Xinjian TianDepartment of Medicinal Chemistry, School of Pharmacy, Fudan University, Shanghai, China.
Jie HuDepartment of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.
Yijun SongDepartment of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.
Xufen YuDepartment of Medicinal Chemistry, School of Pharmacy, Fudan University, Shanghai, China.ORCID http://orcid.org/0000-0001-7794-7890
Fei ZhouDepartment of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.ORCID http://orcid.org/0000-0002-5865-0052
Caicun ZhouDepartment of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China. caicunzhou@163.com.
Xin CaoInstitute of Clinical Sciences, Zhongshan Hospital, Fudan University, Shanghai, China. caox@fudan.edu.cn.ORCID http://orcid.org/0000-0003-1722-023X
Mei WangDepartment of Geriatrics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. wmm0723@126.com.
Qihong HuangCancer Center, Zhongshan Hospital, Fudan University, Shanghai, China. qihong_huang@fudan.edu.cn.ORCID http://orcid.org/0000-0001-6083-710X

Funding

Ministry of Science and Technology of the People's Republic of China (Chinese Ministry of Science and Technology) 2021YFA0804700National Natural Science Foundation of China (National Science Foundation of China) 81872358National Natural Science Foundation of China (National Science Foundation of China) 82072913National Natural Science Foundation of China (National Science Foundation of China) 8230101506Taishan Scholar Foundation of Shandong Province tsqnz20230632
6 · The paper itself

Abstract

Epithelial-mesenchymal transition drives tumor metastasis and therapeutic resistance, yet few treatments have been developed that target this process. Here, we show that ELMO2 represents a specific vulnerability in mesenchymal-like cells. ELMO2 suppression induces excessive autophagy and cell death via FAK activity inhibition. We identify ELMO3 as a functional paralog that compensates for ELMO2 loss, establishing a synthetic lethal interaction. The epithelial-mesenchymal transition core regulator ZEB1 represses ELMO3 transcription in mesenchymal-like cells, rendering them sensitive to ELMO2 blockade. ELMO3 is significantly downregulated in epithelial-mesenchymal transition-associated EGFR inhibitor-resistant cells. Furthermore, the survival of these resistant, mesenchymal-like cells depends on ELMO2/FAK signaling. Through structure-based screening, we identify C52, a small-molecule ELMO2 inhibitor that effectively kills ELMO3-low lung cancer cells and EGFR inhibitor-resistant cells. Our study uncovers an ELMO2-ELMO3 synthetic lethal interaction and establishes ELMO2 as a potential therapeutic target for mesenchymal-like cancer and drug-resistant non-small cell lung cancer.

Indexed as

Adaptor Proteins, Signal TransducingCarcinoma, Non-Small-Cell LungDrug Resistance, NeoplasmEpithelial-Mesenchymal TransitionLung NeoplasmsAnimalsAntineoplastic AgentsAutophagyCell Line, TumorErbB ReceptorsGene Expression Regulation, NeoplasticHumansSignal TransductionZinc Finger E-box-Binding Homeobox 1Adaptor Proteins, Signal TransducingAntineoplastic AgentsErbB ReceptorsZEB1 protein, humanZinc Finger E-box-Binding Homeobox 1

Identifiers

PMID41997974
PMCPMC13276239

What OpenQuestion holds

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LicenceCC BY-NC-ND
Read underepoch 390

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.