Evidence map›Paper›PMID 40476449›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025

LIMK1 as a Novel Kinase of β-Catenin Promotes Esophageal Cancer Metastasis by Cooperating With CDK5.

Shu-Jun Li, Zhuo-Ran Liang, Zhi-Chao Liu, Xue-Ping Luo, Jun-Yi Li, Xiao-Mei Yu, Xuan-Zhang Huang, Yan He, Tao-Yang Xu, Jiao-Jiao Xu and 18 more

Abstract read
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Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

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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

7 citing papers in PubMed.

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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

28 authors.

Shu-Jun LiState Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, 511495, China.
Zhuo-Ran LiangState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, The First Affiliated Hospital (College of Clinical Medicine) of Henan University of Science and Technology, Guangzhou, 510060, China.
Zhi-Chao LiuDepartment of Thoracic Surgery, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200030, China.
Xue-Ping LuoDepartment of Thoracic Surgery, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, 511495, China.
Jun-Yi LiState Key Laboratory of Respiratory Disease, Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510700, China.
Xiao-Mei YuState Key Laboratory of Respiratory Disease, Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510700, China.
Xuan-Zhang HuangDepartment of Surgical Oncology and General Surgery, The First Hospital of China Medical University, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, Shenyang, 110001, China.
Yan HeState Key Laboratory of Respiratory Disease, Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510700, China.
Tao-Yang XuState Key Laboratory of Respiratory Disease, Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510700, China.
Jiao-Jiao XuState Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, 511495, China.
Shao-Cong PengState Key Laboratory of Respiratory Disease, Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510700, China.
Yu-Xiang SongState Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, 511495, China.
Yan HeState Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, 511495, China.
Xiao-Wan ZhuangState Key Laboratory of Respiratory Disease, Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510700, China.
Can-Can ZhengState Key Laboratory of Respiratory Disease, Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510700, China.
Fan ZhangDepartment of Gastrointestinal Surgery, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510700, China.
Alfred King-Yin LamCancer Molecular Pathology and Griffith Medical School, Griffith University, Gold Coast, Queensland, 4222, Australia.
Wei DaiDepartment of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, 999077, China.
Ming-Liang HeDepartment of Biomedical Sciences, City University of Hong Kong, Hong Kong, 999077, China.
Bo LiuFujian Key Laboratory of Precision Medicine for Cancer, Department of Thoracic Surgery, Palmar Hyperhidrosis Research Institute, First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, 350005, China.
Qi ZhaoFaculty of Health Sciences, University of Macau, Macau SAR, 999078, China.
Guo-Liang LuAuckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, and Maurice Wilkins Centre, The University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand.
Jin-Bao LiuState Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, 511495, China.
Zhen-Ning WangDepartment of Surgical Oncology and General Surgery, The First Hospital of China Medical University, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, Shenyang, 110001, China.
Zhi-Gang LiDepartment of Thoracic Surgery, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200030, China.
Ze-Xian LiuState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, The First Affiliated Hospital (College of Clinical Medicine) of Henan University of Science and Technology, Guangzhou, 510060, China.
Wen-Wen XuState Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, 511495, China.
Bin LiState Key Laboratory of Respiratory Disease, Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510700, China.ORCID https://orcid.org/0000-0002-8979-610X

Funding

Guangdong Natural Science Research International joint project 2023A0505050165Guangdong Natural Science Research International joint project 2025A1515010195Guangzhou Education Bureau Yangcheng Scholar Research Project 202235385key disciplines of medicine of Guangzhou 2025-2027Key Laboratory of Guangdong Higher Education Institutes 2021KSYS009National Key R&D Program of China 2021YFA1302100National Natural Science Foundation of China 32370698National Natural Science Foundation of China 82204455National Natural Science Foundation of China 82273141National Natural Science Foundation of China 82273368National Outstanding Youth Science Fund Project of National Natural Science Foundation of China 2023B1515020012Science and Technology Program of Guangzhou 2023A03J0425Science and Technology Program of Guangzhou 2025A03J3287Science and Technology Program of Guangzhou 2025A03J3288Science and Technology Program of Guangzhou 2025A04J3563Young Talents Program of Sun Yat-sen University Cancer Center YTP-SYSUCC-0029
6 · The paper itself

Abstract

Metastasis is a major cause of cancer deaths, but the underlying molecular mechanisms remain largely unknown. Esophageal squamous cell carcinoma (ESCC) is a highly aggressive cancer with poor survival, yet the key kinases driving ESCC metastasis and their biological function have not been fully discovered. Here, a kinase-substrate map of metastatic ESCC is presented for the first time by conducting a phosphoproteomics analysis of 60 clinical specimens. By further consolidating data with CRISPR/Cas9 functional screening, LIM domain kinase 1 (LIMK1) is identified as a novel kinase of β-catenin. The in vitro and in vivo experiments demonstrated that LIMK1 cooperates with Cyclin-dependent kinase 5 (CDK5) to promote cancer metastasis in a phosphorylation-dependent manner. Mechanistically, LIMK1 and CDK5 synergistically phosphorylate β-catenin at S191, enhancing its phosphorylation and interaction with Nucleoporin 93, resulting in β-catenin nuclear translocation and activation of key pathways in cancer metastasis. High expression of LIMK1 and CDK5 is associated with poor prognosis of ESCC patients, and the clinical and functional significance of LIMK1/CDK5-Wnt/β-catenin axis is also verified in esophageal adenocarcinoma, gastric cancer, and lung cancer. Furthermore, the combination of LIMK1 and CDK5 inhibitors significantly suppresses metastasis in multiple models. This work highlights LIMK1 as a novel regulatory and targetable kinase of β-catenin, informing the treatment of advanced cancer.

Indexed as

beta CateninCyclin-Dependent Kinase 5Esophageal NeoplasmsEsophageal Squamous Cell CarcinomaLim KinasesAnimalsCell Line, TumorFemaleHumansMaleMiceNeoplasm MetastasisPhosphorylationbeta CateninCDK5 protein, humanCTNNB1 protein, humanCyclin-Dependent Kinase 5LIMK1 protein, humanLim Kinasesesophageal squamous cell carcinomakinase‐substrate mapLIMK1metastasisβ‐catenin

Identifiers

PMID40476449
PMCPMC12362812

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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.