The liver exhibits the highest recovery rate from acute injuries. However, in chronic liver disease, the long-term loss of hepatocytes often leads to adverse consequences such as fibrosis, cirrhosis, and liver cancer. The Wnt signaling plays a pivotal role in both liver regeneration and tumorigenesis. Therefore, manipulating the Wnt signaling has become an attractive approach to treating liver disease, including cancer. Nonetheless, given the crucial roles of Wnt signaling in physiological processes, blocking Wnt signaling can also cause several adverse effects. Recent studies have identified cancer-specific regulators of Wnt signaling, which would overcome the limitation of Wnt signaling target approaches. In this review, we discussed the role of Wnt signaling in liver regeneration, precancerous lesion, and liver cancer. Furthermore, we summarized the basic and clinical approaches of Wnt signaling blockade and proposed the therapeutic prospects of cancer-specific Wnt signaling blockade for liver cancer treatment.
Citations
Citations to this article as recorded by
Correspondence to letter to the editor on “GULP1 as a novel diagnostic and predictive biomarker in hepatocellular carcinoma” Hyung Seok Kim, Soon Sun Kim, Jae Youn Cheong, Jung Woo Eun Clinical and Molecular Hepatology.2026; 32(1): e103. CrossRef
Intestinal LKB1 Loss Drives a Premalignant Program Along the Serrated Cancer Pathway S.F. Plugge, H. Ma, J.Y. van der Vaart, J. Sprangers, F.H.M. Morsink, D. Xanthakis, C. Jamieson, K.B.W. Stroot, A.R. Keijzer, T. Margaritis, T. Candelli, R. Straver, J. de Ridder, F.C.P. Holstege, W.W.J. de Leng, G.J.A. Offerhaus, A. Merenda, M.M. Maurice Gastroenterology.2026; 170(2): 298. CrossRef
Regulation of Keratin Chemical Modifications: Potential Molecular Mechanisms in Proliferative Diseases Xuemei Ma, Xiaoli Jiang, Mengxue Song, Bingbing Bai, Xia Hou, Qingtian Wu International Journal of Molecular Sciences.2026; 27(2): 972. CrossRef
Overview of two similar modification: O-GlcNAc and O-GalNAc modifications Bo Xu, Tao Zhang, Siqi Huang, Yiming Wang, Long Wang, Yanting Su Carbohydrate Research.2026; 564: 109905. CrossRef
The “Direct Structural Disruption” Hypothesis: Bacteroides fragilis Toxin as a Potentiating Cofactor in MASH Pathogenesis Ju-Eun Hong, Soonjae Hwang Toxins.2026; 18(5): 200. CrossRef
Cross-Organ Toxicity and Metabolic Responses to Food Chain-Transferred Nanoplastics: Mechanistic Insights from a Multiomics Perspective Xiaochuan Qu, Yutian Shi, Yuheng Li, Yuewen Han, Guoming Sun, Huayang Sun, Yijing Wang, Xinrui Nan, Ruixuan Qu, Ning Zhang, Xin Zhao, Baoqin Liu ACS Nano.2026; 20(20): 14426. CrossRef
Histone Methylation: A Pivotal Epigenetic Driver of the Malignant Transformation of MASLD-HCC Yan Zhang, Tong Chen, Zhanjie Chang, Xinlei Qi, Ruijuan Yan, Haibo Zhang, Xi Guan, Shuguang Yan, Jingtao Li, Junzhe Jiao Journal of Hepatocellular Carcinoma.2026; Volume 13: 1. CrossRef
Blood flow‐induced angiocrine signals promote organ growth and regeneration Paula Follert, Linda Große‐Segerath, Eckhard Lammert BioEssays.2025;[Epub] CrossRef
In vitro β-catenin attenuation by a mefloquine-loaded core–shell nano emulsion strategy to suppress liver cancer cells Priyadarshini Mohapatra, Natarajan Chandrasekaran Nanoscale Advances.2025; 7(3): 748. CrossRef
YAP/TAZ as master regulators in liver regeneration and disease: insights into mechanisms and therapeutic targets Bingyu Ye, Meijuan Yue, Hu Chen, Caifang Sun, Yongle Shao, Qinpeng Jin, Chunyan Zhang, Guoying Yu Molecular Biology Reports.2025;[Epub] CrossRef
Protein Coronation-Induced Cancer Staging-Dependent Multilevel Cytotoxicity: An All-Humanized Study in Blood Vessel Organoids Chan Wang, Yingyi Quan, Jiang Jiang, Han Yu, Jia Liu, Wei Tang, Xinyue Li, Shouju Wang, Da Huo, Guang-Liang Jiang, Yang Yang, Qingqing Ding ACS Nano.2025; 19(1): 345. CrossRef
Wnt Pathway-Targeted Therapy in Gastrointestinal Cancers: Integrating Benchside Insights with Bedside Applications Anirudh Nayak, Hannah Streiff, Ivan Gonzalez, Oluwabomi Oluwatomi Adekoya, Itzcoatl Silva, Anitha Kota Shenoy Cells.2025; 14(3): 178. CrossRef
Molecular mechanisms in liver repair and regeneration: from physiology to therapeutics Xiao Ma, Tengda Huang, Xiangzheng Chen, Qian Li, Mingheng Liao, Li Fu, Jiwei Huang, Kefei Yuan, Zhen Wang, Yong Zeng Signal Transduction and Targeted Therapy.2025;[Epub] CrossRef
Cell competition as an emerging mechanism and therapeutic target in cancer Dakai Yang, Wenyue Sun, Lu Gao, Kai Zhao, Qin Zhuang, Yun Cai Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease.2025; 1871(5): 167769. CrossRef
Wnt signaling pathways in biology and disease: mechanisms and therapeutic advances Chen Xue, Qingfei Chu, Qingmiao Shi, Yifan Zeng, Juan Lu, Lanjuan Li Signal Transduction and Targeted Therapy.2025;[Epub] CrossRef
Influencing factors and mechanism of hepatocyte regeneration Xiaoyi Zhang, Shenghao Li, Liyuan Hao, Fukang Jia, Fei Yu, Xiaoyu Hu Journal of Translational Medicine.2025;[Epub] CrossRef
AEBP1 or ACLP, which is the key factor in inflammation and fibrosis? Zhang Runtian, Han Wenqiang, Shen Zimeng, Wang Tianyu, Zhong Jingquan International Journal of Biological Macromolecules.2025; 310: 143554. CrossRef
Nicotinamide N-Methyltransferase (NNMT) and Liver Cancer: From Metabolic Networks to Therapeutic Targets Shi-Yan Lai, Xiao-Juan Zhu, Wei-Dong Sun, Shuang-Zhou Bi, Chen-Ying Zhang, An Liu, Jiang-Hua Li Biomolecules.2025; 15(5): 719. CrossRef
Glycyrrhizic acid promotes liver regeneration through activating β-catenin in acetaminophen-induced liver injury Rong Cao, Hui Gong, Shuang Xia, Zhiyu Hu, Xiaoxiang Fan, Bowen Zhai, Linna Guo, Chunguang Xia, Zhichao Jiang, Miao Yan Journal of Ethnopharmacology.2025; 349: 119895. CrossRef
The Association Between Hepatocellular Carcinoma and Gastrointestinal Adenocarcinoma: Is This a New Syndrome in Patients With Cirrhosis? A Case Series Fabrizio Bronte, Fabio D'Amato, Maria Rosa Barcellona, Giuseppe Bronte, Giuseppe Malizia, Salvatore Ialuna, Giorgio Fusco, Francesco Verderame, Enrico Bronte, Maria Grazia Bavetta Cancer Reports.2025;[Epub] CrossRef
The protective role of vitamin C against linezolid-induced hepato-renal toxicity in a rat model Shaimaa M. Azzam, Hend Mohamed Anwar, Ahmed H. Abd El-Slam, Marwa S. M. Diab, Halima Mohamed Ibrahim, Abdalrahman Mohammed Yousef, Fatma Mahmoud Sabry, Ibrahim A. Darwish, Kalidasan Kaliyamoorthy, Gad Elsayed Mohamed Salem, Heba M. A. Elsanhory Frontiers in Pharmacology.2025;[Epub] CrossRef
High-efficient discovering the potent anti-Notum agents from herbal medicines for combating glucocorticoid-induced osteoporosis Yuqing Song, Feng Zhang, Jia Guo, Yufan Fan, Hairong Zeng, Mengru Sun, Jun Qian, Shenglan Qi, Zihan Chen, Xudong Jin, Yunqing Song, Tian Tian, Zhi Qian, Yao Sun, Zhenhao Tian, Baoqing Yu, Guangbo Ge Acta Pharmaceutica Sinica B.2025; 15(8): 4174. CrossRef
Matrine targets β-catenin and blocks the formation of β-catenin/TCF7L2 complex to promote ferroptosis and inhibit metastasis in triple-negative breast cancer Yazhou Sang, Yue Hu, Ruohan Liang, Yueyue Zhang, Hongyuan Du, Huilan Zhang, Juan Chen, Yaqiong Zhang, Xuan Cao Phytomedicine.2025; 145: 157044. CrossRef
Advances in the Study of RNA Deconjugating Enzyme DDX5 in Cancer 静 宋 World Journal of Cancer Research.2025; 15(03): 124. CrossRef
SERPINH1 promotes malignant progression of laryngeal squamous cell carcinoma via COL7A1-mediated Wnt/β-catenin signaling Feinan He, Jinqiu Li, Weifang Tong, Sanchun Wang, Hongyan Wang, Baishuo Huang, Bo Teng Cellular Signalling.2025; 135: 112043. CrossRef
Liver regeneration after partial hepatectomy: Triggers and mechanisms Bakari Korchilava, Tamar Khachidze, Nino Megrelishvili, Lika Svanadze, Manana Kakabadze, Keti Tsomaia, Memed Jintcharadze, Dimitri Kordzaia World Journal of Hepatology.2025;[Epub] CrossRef
Targeting Wnt-driven metabolic adaptations in cancer: integrating glycolysis, glutaminolysis, IDO1-mediated immune evasion, and therapeutic delivery strategies Eric Flores-Hernández, Grace Binder, Kuo-Ching Mei, Nydia Tejeda-Muñoz Frontiers in Cell and Developmental Biology.2025;[Epub] CrossRef
Therapeutic Advances in Signaling Channels and Their Associated Targets in the Development of Liver Fibrosis 芳卓 朱 Journal of Clinical Personalized Medicine.2025; 04(05): 48. CrossRef
WNT signaling in cancer: molecular mechanisms and potential therapies Jiaqi Liang, Yiming Pan, Jingru Yang, Dequan Zeng, Jing Li Molecular Biomedicine.2025;[Epub] CrossRef
Clinicopathological insights and management of liver metastases: Current advances and future perspectives Noura A A Ebrahim, Thoraya A Farghaly, Ahmed Abdo El-Sherif, Ahmed M Fahmy, Moamen O Othman, Neveen S Tahoun, Omnia Mohamed Korany, Aya Arafat, Reham Oreaba, Soliman M A Soliman World Journal of Hepatology.2025;[Epub] CrossRef
Elucidating the role of SIRT2 in hepatocellular carcinoma through multi-omics and deep learning Changan Chen, Tingmei Yang, Caiyuan Yu, Lijiao Cui, Bingjun Cai, Zhenkai Li, Shicai Ye, Yijie Weng Discover Oncology.2025;[Epub] CrossRef
Conversion Therapy and Liver Regeneration in Liver Cancer Xiaoqin Wu Journal of Biosciences and Medicines.2025; 13(12): 374. CrossRef
Signaling pathways of liver regeneration: Biological mechanisms and implications Chunyan Zhang, Caifang Sun, Yabin Zhao, Bingyu Ye, GuoYing Yu iScience.2024; 27(1): 108683. CrossRef
miR-199a-5p modulates choroidal neovascularization by regulating Wnt7b/Wnt/β-catenin signaling pathway Yu Geng, HaiRong Hua, Yuan Xia, Jie Zhou, Jian He, XingYu Xu, JianFeng Zhao Journal of Molecular Histology.2024; 55(3): 359. CrossRef
Unraveling the crosstalk: circRNAs and the wnt signaling pathway in cancers of the digestive system Yu Zhang, Cheng Zhang, Chuanhui Peng, Junjun Jia Non-coding RNA Research.2024; 9(3): 853. CrossRef
Advances in precision gene editing for liver fibrosis: From technology to therapeutic applications Peng Ji, Yan Li, Zihan Wang, Siyu Jia, Xinyi Jiang, Hui Chen, Qun Wang Biomedicine & Pharmacotherapy.2024; 177: 117003. CrossRef
HNF4α improves hepatocyte regeneration by upregulating PXR Shantong Qiu, Yangyang Pan, Yan Cui, Mei Li, Tao Yue, Sisi Pu, Qian Zhang, Meng Wang The FASEB Journal.2024;[Epub] CrossRef
A male mouse model for metabolic dysfunction-associated steatotic liver disease and hepatocellular carcinoma Byung-Kwan Jeong, Won-Il Choi, Wonsuk Choi, Jieun Moon, Won Hee Lee, Chan Choi, In Young Choi, Sang-Hyun Lee, Jung Kuk Kim, Young Seok Ju, Pilhan Kim, Young-Ah Moon, Jun Yong Park, Hail Kim Nature Communications.2024;[Epub] CrossRef
Unveiling the anticancer effect of traditional Chinese herbal medicine Naoki Asano World Journal of Gastroenterology.2024; 30(30): 3626. CrossRef
Unveiling the anticancer effect of traditional Chinese herbal medicine Naoki Asano World Journal of Gastroenterology.2024; 30(30): 3625. CrossRef
Novel biomarkers and drug correlations of non-canonical WNT signaling in prostate and breast cancer Yongming Huang, Meiyin Fan, Yushuai Liu, Xiaoying Jiang, Kevin Du, Alice Wu, Qingyi Li, Yingying Wu, Jiaqian Liang, Keshan Wang Discover Oncology.2024;[Epub] CrossRef
NSUN2 regulates Wnt signaling pathway depending on the m5C RNA modification to promote the progression of hepatocellular carcinoma Huiwu Xing, Xinyu Gu, Yingru Liu, Lixia Xu, Yuting He, Chen Xue Oncogene.2024; 43(47): 3469. CrossRef
Discovery of CLKs inhibitors for the treatment of non-small cell lung cancer Tianxing Hu, Jiali Huang, Rui Chen, Hui Zhang, Mai Liu, Renbing Wang, Wenyi Zhou, Dechun Huang, Mingkang Cao, Depeng Li, Zhiyu Li, Hongxi Wu, Jinlei Bian European Journal of Medicinal Chemistry.2024; 280: 116952. CrossRef
Roles of deubiquitinases in urologic cancers (Review) Liangpei Wu, Jiahui Wang, Lin Chai, Jun Chen, Xiaofeng Jin Oncology Letters.2024;[Epub] CrossRef
Modulation of the central nervous system immune response and neuroinflammation via Wnt signaling in health and neurodegenerative diseases Kevin Fang Ibrain.2024; 10(4): 462. CrossRef
Yiqi Liangxue Jiedu Prescription Inhibited the Canonical Wnt Pathway to Prevent Hepatocellular Precancerous Lesions Yuling Liang, Yuqing Xie, Zhibo Dang, Mengge Li, Lihua Yu, Xinhui Wang, Peng Wang, Zhiyun Yang Journal of Hepatocellular Carcinoma.2024; Volume 11: 2293. CrossRef
Wnt Signaling Activation in Gingival Epithelial Cells and Macrophages of Experimental Periodontitis Ying Chen, Yang Hu Dentistry Journal.2023; 11(5): 129. CrossRef
Targeting signaling pathways in osteosarcoma: Mechanisms and clinical studies Ziyu Ji, Jianlin Shen, Yujian Lan, Qian Yi, Huan Liu MedComm.2023;[Epub] CrossRef
Therapeutic strategies to improve liver regeneration after hepatectomy Hayeong Jeong, Chanbin Lee, Min Jae Lee, Youngmi Jung Experimental Biology and Medicine.2023; 248(15): 1313. CrossRef
Integrated analysis of tumor microenvironment features to establish a diagnostic model for papillary thyroid cancer using bulk and single-cell RNA sequencing technology Yizeng Wang, Wenbin Song, Yingxi Li, Zhaoyi Liu, Ke Zhao, Lanning Jia, Xiaoning Wang, Ruoyu Jiang, Yao Tian, Xianghui He Journal of Cancer Research and Clinical Oncology.2023; 149(18): 16837. CrossRef
Milk thistle nano-micelle formulation promotes cell cycle arrest and apoptosis in hepatocellular carcinoma cells through modulating miR-155-3p /SOCS2 /PHLDA1 signaling axis Saghar Rahnama, Zahra Moazezi Tehrankhah, Fatemeh Mohajerani, Faezeh Shah Mohammadi, Zahra Yousefi Yeganeh, Farhood Najafi, Sadegh Babashah, Majid Sadeghizadeh BMC Complementary Medicine and Therapies.2023;[Epub] CrossRef
Associations of Wnt5a expression with liver injury in chronic hepatitis B virus infection Xiang-Fen Ji, Qi Zhou, Jing-Wei Wang, Fei Sun, Shuai Gao, Kai Wang BMC Infectious Diseases.2023;[Epub] CrossRef
Unveiling the power of microenvironment in liver regeneration: an in-depth overview Yuelei Hu, Ruilin Wang, Ni An, Chen Li, Qi Wang, Yannan Cao, Chao Li, Juan Liu, Yunfang Wang Frontiers in Genetics.2023;[Epub] CrossRef
First
Prev
