Evidence map›Paper›PMID 41882657›Full record

ArticleCancer cell international2026

Integrating multi-omics data revealing LIMK1 as a metastatic biomarker in LUAD patients with brain metastasis.

Changqing Yang, Jianjian Ying, Cangchang Shi, Linyue Hai, Guixin Wang, Yingxi Li, Yao Tian, Jinxian He, Keyun Zhu, Jing Feng

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

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5 · Who and what money

Authors and funding

10 authors.

Changqing Yang *Department of Respiratory and Critical Care Medicine, Tianjin Medical University General Hospital, Tianjin, 300052, China.
Jianjian Ying *Department of Thoracic Surgery, The Affiliated LiHuiLi Hospital of Ningbo University, Ningbo, 315040, Zhejiang, China.
Cangchang ShiDepartment of Respiratory and Critical Care Medicine, Tianjin Medical University General Hospital, Tianjin, 300052, China.
Linyue HaiThe First Department of Breast Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Breast Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, 300060, China.
Guixin WangThe First Department of Breast Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Breast Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, 300060, China.
Yingxi LiHealth Science Center, Ningbo University, Ningbo, 315211, Zhejiang, China.
Yao TianDepartment of Thoracic Surgery, The Affiliated LiHuiLi Hospital of Ningbo University, Ningbo, 315040, Zhejiang, China.
Jinxian HeDepartment of Thoracic Surgery, The Affiliated LiHuiLi Hospital of Ningbo University, Ningbo, 315040, Zhejiang, China.
Keyun ZhuDepartment of Thoracic Surgery, The Affiliated LiHuiLi Hospital of Ningbo University, Ningbo, 315040, Zhejiang, China. lhlzhukeyun@nbu.edu.cn.
Jing FengDepartment of Respiratory and Critical Care Medicine, Tianjin Medical University General Hospital, Tianjin, 300052, China. tmugh_fj@tmu.edu.cn.

Funding

National Natural Science Foundation of China 82170097Ningbo Natural Science Foundation 2023J226The Medical Science and Technology Project of Zhejiang Province 2024KY284Tianjin Key Medical Discipline Construction Project TJYXZDXK-3-004C
6 · The paper itself

Abstract

backgroundLung adenocarcinoma (LUAD) is a major subtype of lung cancer that frequently develops brain metastases. Tumor heterogeneity substantially complicates disease management, and reliable biomarkers for metastatic progression remain lacking. LIM domain kinase 1 (LIMK1), a key regulator of cytoskeletal dynamics, has been implicated in tumor progression; however, its role in regulating brain metastasis in LUAD remains unclear.

methodsSingle-cell RNA sequencing data from 11 primary LUAD tumors and 10 brain metastases were analyzed to identify malignant epithelial subclusters associated with metastatic dissemination. Tumor evolutionary trajectories and gene regulatory networks were explored using pseudotime trajectory analysis and weighted gene co-expression network analysis. LIMK1 expression was validated using The Cancer Genome Atlas dataset, as well as RT–qPCR and Western blotting in LUAD tissues and cell lines. Functional assays, including cell proliferation, colony formation, migration, and invasion, were performed following LIMK1 knockdown in LUAD cell lines.

resultsSix malignant epithelial subclusters were identified, among which clusters 0 and 4 were significantly enriched in brain metastases and associated with poor survival outcomes. LIMK1 was identified as a hub gene within these metastasis-associated clusters. LIMK1 expression was markedly upregulated in LUAD tissues and cell lines, and elevated LIMK1 levels predicted an unfavorable prognosis. Functional experiments demonstrated that LIMK1 depletion significantly inhibited tumor cell proliferation, migration, and invasion, while partially reversing epithelial–mesenchymal transition (EMT). Mechanistically, LIMK1 was found to promote LUAD progression through activation of the PI3K/AKT/mTOR signaling pathway.

conclusionsLIMK1 represents a novel prognostic biomarker and metastasis-associated regulator in LUAD. By driving EMT and activating PI3K/AKT/mTOR signaling, LIMK1 facilitates malignant progression, highlighting its potential as a therapeutic target for LUAD patients with brain metastases.

Indexed as

brain metastasisLIMK1lung adenocarcinomamulti-omicstumor heterogeneity

Identifiers

PMID41882657
PMCPMC13137581

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