The DOI matches its Crossref record; 50 of the 50 references it cites were found in a registry or an index.
Niclosamide Suppresses Cancer Cell Growth By Inducing Wnt Co-Receptor LRP6 Degradation and Inhibiting the Wnt/β-Catenin Pathway
Open accessAbstract
The Wnt/β-catenin signaling pathway is important for tumor initiation and progression. The low density lipoprotein receptor-related protein-6 (LRP6) is an essential Wnt co-receptor for Wnt/β-catenin signaling and represents a promising anticancer target. Recently, the antihelminthic drug, niclosamide was found to inhibit Wnt/β-catenin signaling, although the mechanism was not well defined. We found that niclosamide was able to suppress LRP6 expression and phosphorylation, block Wnt3A-induced β-catenin accumulation, and inhibit Wnt/β-catenin signaling in HEK293 cells. Furthermore, the inhibitory effects of niclosamide on LRP6 expression/phosphorylation and Wnt/β-catenin signaling were conformed in human prostate PC-3 and DU145 and breast MDA-MB-231 and T-47D cancer cells. Moreover, we showed that the mechanism by which niclosamide suppressed LRP6 resulted from increased degradation as evident by a shorter half-life. Finally, we demonstrated that niclosamide was able to induce cancer cell apoptosis, and displayed excellent anticancer activity with IC(50) values less than 1 µM for prostate PC-3 and DU145 and breast MDA-MB-231 and T-47D cancer cells. The IC(50) values are comparable to those shown to suppress the activities of Wnt/β-catenin signaling in prostate and breast cancer cells. Our data indicate that niclosamide is a unique small molecule Wnt/β-catenin signaling inhibitor targeting the Wnt co-receptor LRP6 on the cell surface, and that niclosamide has a potential to be developed a novel chemopreventive or therapeutic agent for human prostate and breast cancer.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“In our previous studies, we have demonstrated that niclosamide (5-chloro-N-[2-chloro-4-nitrophenyl]−2-hydroxy benzamide), an FDA approved antihelminthic drug, suppresses Wnt/β-catenin signaling by promoting Wnt co-receptor LRP6 degradation in cancer cells [27, 37, 38].”
From CI-994 is a dual modulator of class I HDACs and Wnt/β-catenin signaling for the treatment of Alzheimer's disease (2026) · cites this paper as [27]
The cited source says what the claim attributes to it.
In the citing paper
“On the other hand, niclosamide can induce Wnt co-receptor LRP6 degradation and suppress Wnt/β-catenin signaling in cancer cells [27, 37, 38], while CI-994 displays the opposite effect on LRP6 regulation by reducing LRP6 turnover.”
From CI-994 is a dual modulator of class I HDACs and Wnt/β-catenin signaling for the treatment of Alzheimer's disease (2026) · cites this paper as [27]
The cited source says what the claim attributes to it.
In the citing paper
“On the other hand, niclosamide can induce Wnt co-receptor LRP6 degradation and suppress Wnt/β-catenin signaling in cancer cells [27, 37, 38], while CI-994 displays the opposite effect on LRP6 regulation by reducing LRP6 turnover.”
From CI-994 is a dual modulator of class I HDACs and Wnt/β-catenin signaling for the treatment of Alzheimer's disease (2026) · cites this paper as [27]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Wnt/β-Catenin Signaling: Components, Mechanisms, and Diseases
MacDonald, B. T., Tamai, K., & He, X. (2009) · Developmental Cell · doi:10.1016/j.devcel.2009.06.016 · Cited by 5,583
β-Catenin regulates expression of cyclin D1 in colon carcinoma cells
Tetsu, O., & McCormick, F. (1999) · Nature · doi:10.1038/18884 · Cited by 3,601
Identification of Selective Inhibitors of Cancer Stem Cells by High-Throughput Screening
Gupta, P. B., Önder, T. T., Jiang, G., Tao, K. X., Kuperwasser, C., Weinberg, R. A., & Lander, E. S. (2009) · Cell · doi:10.1016/j.cell.2009.06.034 · Cited by 2,429
The cyclin D1 gene is a target of the β-catenin/LEF-1 pathway
Shtutman, M., Zhurinsky, J., Simcha, I., Albanese, C., D’Amico, M., Pestell, R., & Ben-Ze’ev, A. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.10.5522 · Cited by 2,230
Jho, E., Zhang, T., Domon–Dell, C., Joo, C., Freund, J., & Costantini, F. D. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.4.1172-1183.2002 · Cited by 1,683
Lustig, B., Jerchow, B., Sachs, M., Weiler, S., Pietsch, T., Karsten, U., van de Wetering, M., Clevers, H., Schlag, P., Birchmeier, W., et al. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.4.1184-1193.2002 · Cited by 1,198
LDL-receptor-related proteins in Wnt signal transduction
Tamai, K., Semenov, M., Kato, Y., Spokony, R., Liu, C., Katsuyama, Y., Hess, F., Saint-Jeannet, J.-P., & He, X. (2000) · Nature · doi:10.1038/35035117 · Cited by 1,128
An LDL-receptor-related protein mediates Wnt signalling in mice
Pinson, K. I., Brennan, J., Monkley, S. J., Avery, B. J., & Skarnes, W. C. (2000) · Nature · doi:10.1038/35035124 · Cited by 1,086
Epigenetic inactivation of SFRP genes allows constitutive WNT signaling in colorectal cancer
Suzuki, H., Watkins, D. N., Jair, K.-W., Schuebel, K. E., Markowitz, S. D., Chen, W. D., Pretlow, T. P., Yang, B., Akiyama, Y., van Engeland, M., et al. (2004) · Nature Genetics · doi:10.1038/ng1330 · Cited by 1,074
Targeting cancer stem cells by inhibiting Wnt, Notch, and Hedgehog pathways
Takebe, N., Harris, P. J., Warren, R. Q., & Ivy, S. P. (2010) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2010.196 · Cited by 1,025
Flagged first, then by citations
Cited by
Sorted by citations
Items 201–231 of 231
Jiang, H., Tiche, S. J., He, C. J., Jedoui, M., Forgo, B. L., Zhao, M., He, B., Li, Y., Li, A. M., Truong, A. T., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.01.22.576741 · Cited by 2
“In several studies, niclosamide or NEN alone had anti-tumor effects in a variety of in vitro and preclinical tumor models [40-44].”
BackgroundSelf-citationDesloratadine Induces TP53-Dependent Apoptosis in MCF-7 Breast Cancer Cells
Kabir, S. R., Abdullah, T., Azam, G., Molla, T. H., Ali, H., Miah, M., Alam, M. T., & Miah, S. (2025) · Cells · doi:10.3390/cells14211725 · Cited by 1
Immunohistochemical Expression of Wnt-4 Protein in Clear Cell Renal Carcinoma
Pavlović, O., Hudolin, T., Miškulin, I., Bulimbašić, S., Ćorić, M., Perković, J., & Zekulić, T. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10245795 · Cited by 1
Recent Advances in Wnt/β-Catenin Pathway Small-Molecule Inhibitors
Holsworth, D. D., & Krauss, S. J. K. (2012) · Annual reports in medicinal chemistry · doi:10.1016/b978-0-12-396492-2.00026-6 · Cited by 1
Therapeutic Targetingof the Wnt Signaling Network
Rudge, F., & Dale, T. C. (2014) · Wiley eBooks · doi:10.1002/9781118444122.ch32 · Cited by 1
Schumacher, T., Iyer, A. V., Rumbley, J. N., Ronayne, C. T., & Mereddy, V. R. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.05.02.592272 · Cited by 1
“In the past decade, increasing interest in leveraging niclosamide as an anticancer agent has led to the discovery that niclosamide targets a wide range of pathways such as regulation of Wnt/ -catenin 18,19 , mTORC1 20–22 , STAT3 23–25 , NF- B 25,26 , and Notch signaling pathways.”
BackgroundTargeting Key Stemness-Related Pathways in Human Cancers
Coyle, K. M., Thomas, M. L., Sultan, M., & Marcato, P. (2015) · Springer eBooks · doi:10.1007/978-3-319-21030-8_15
Lawford‐Smith, H. (2015)
Atlas of Genetics and Cytogenetics in Oncology and Haematology
Sherbet, G. V. (2014)
Seow, H. F. (2017) · Advances in Cytology & Pathology · doi:10.15406/acp.2017.02.00021
Targeted Therapies in Breast Cancer
Lyons, A. T., & Prosperi, J. R. (2017) · Resistance to targeted anti-cancer therapeutics · doi:10.1007/978-3-319-70142-4_6
Barghout, S. H. (2015) · ERA: Education and Research Archive (University of Alberta) · doi:10.7939/r36w96f5t
Pharmacological interventions part II
Koltai, T., Reshkin, S. J., & Harguindey, S. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-819059-3.00014-9
Proteolytic processing of LRP6 and its effects on canonical Wnt signaling
Connell, A. J. (2020) · Library, Museums and Press - UDSpace (University of Delaware) · doi:10.58088/zxzv-2g23
The Pharmacology of WNT Signaling
Daskalopoulos, E. P., & Blankesteijn, W. M. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-820472-6.00097-9
(2013) · Elsevier eBooks · doi:10.1016/b978-0-12-416570-0.00043-3
Innovative pharmaceutical strategies for niclosamide repositioning
Barbosa, E. J. (2022) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.9.2022.tde-30112022-110043
An Insight on Colon Cancer Stem Cells and Its Therapeutic Implications
Pournami Gopan, S., Das, A., Esmeeta, A., Deka, D., Duttaroy, A. K., Pathak, S., & Banerjee, A. (2024) · Springer eBooks · doi:10.1007/978-981-99-6263-1_63
Role and Therapeutic Implication of Wnt Signalling Pathway in Cancer
Aga, S. S., Nissar, S., & Banday, M. Z. (2025) · Springer eBooks · doi:10.1007/978-981-96-2763-9_7
Singh, A. K., Gardner, Z. S., Kumpati, G. P., Jacob, M., Ronayne, C. T., & Mereddy, V. R. (2026) · Current Medicinal Chemistry · doi:10.2174/0109298673440168260809163531
Rearrangement of signaling pathways and adaptation of tumor cells to hypoxia
Andreeva, O. E., Mikhaevich, E. I., & Ma, K. (2025) · Advances in molecular oncology · doi:10.17650/2313-805x-2025-12-4-8-23
Rejinold, N. S., Jin, G., & Choy, J. (2026) · Wiley Interdisciplinary Reviews Nanomedicine and Nanobiotechnology · doi:10.1002/wnan.70054
Marchiò, S. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27052400
Lü, W., Caulfield, T. R., Lee, E., Jeevaratnam, S., Wang, N., Bu, G., Kanekiyo, T., & Li, Y. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.04.30.721954
Self-citationAl‐Zoubi, R. M., Farhan, A., Hanbali, B., Al-Zoubi, S. R., Khan, A., Shkoor, M., Bani‐Yaseen, A. D., Zoubi, M. S. A., & Agouni, A. (2026) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2026.118987
Lu, W., Caulfield, T. R., Lee, E., Jeevaratnam, S., Wang, N., Bu, G., Kanekiyo, T., & Li, Y. (2026) · Neurotherapeutics · doi:10.1016/j.neurot.2026.e00974
“The Super8XTOPFlash luciferase assay was conducted in HEK293 cells transiently transfected with the Super8XTOPFlash luciferase construct, pcDNA3-Wnt3-HA and β -galactosidase-expressing vector as described in our previous studies [26,27].”
Self-citationAI-Driven Drug Repurposing Strategies for Precision Therapy in Breast Cancer
Jakkula, B. K., & Shyam, P. (2026) · Pharmaceutical science. · doi:10.5772/intechopen.1016336
Uncovering pan-cancer signatures of chemoresistance
Inayatullah, M., Demirdizen, E., Keepers, Z., Correia, C. M., Hashemi, S. M., Tripathi, K. K., Sadhukhan, S., Bardhan, I., Mariappan, A., Rassool, F. V., et al. (2026) · Genome Medicine · doi:10.1186/s13073-026-01763-2
“To test therapeutic vulnerabilities, we evaluated the effects of specific inhibitors of SRM (SRMi, 4MCHA [58]), MYC (MYCMI-6 [59]), and WNT (Niclosamide [60]) alone and in combination with cisplatin or paclitaxel.”
Drug Repurposing in Cancer Therapy: A Review of Therapeutic Potential Across Diverse Drug Classes
Yadav, V., Mandaliya, V. B., & Shah, U. (2026) · ChemistrySelect · doi:10.1002/slct.202506782
Gribok, A., Pavlidou, M., Li, K., Kim, H., Zhang, K., Deng, C., Carvalho, I., Chou, C., Sims, A., Yee, A. K., et al. (2026) · Targets · doi:10.3390/targets4040032
Metadata
- Authors
- Lu, W., Lin, C., Roberts, M. J., Waud, W. R., Piazza, G. A., & Li, Y.
- Affiliations
- Southern Research Institute (US)
- University of South Alabama (US)
- Corresponding author
- Li, Yonghe
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2011-12-16
- Volume
- 6
- Issue
- 12
- Pages
- e29290
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3241710
- OpenAlex
- W2007145040
- Cited by
- 230
- References
- 50
- Citations by year
- 2026: 14 · 2025: 13 · 2024: 16 · 2023: 10 · 2022: 12 · 2021: 18 · 2020: 22 · 2019: 19 · 2018: 17 · 2017: 20 · 2016: 21 · 2015: 21 · 2014: 14 · 2013: 8 · 2012: 5
- FWCI
- 3.51
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- University of Rochester
- National Institutes of Health (RO1CA124531)
- National Cancer Institute (R01CA124531)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Hedgehog Signaling Pathway Studies
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- niclosamide, LRP6, Wnt/β-catenin signaling, Wnt co-receptor, protein degradation, prostate cancer, breast cancer, apoptosis, anticancer drug repurposing, antihelminthic drugs, chemoprevention
- MeSH terms
- Dishevelled Proteins, Breast Neoplasms, Drug Screening Assays, Antitumor, Female, Humans, Male, Neoplasm Proteins, Neoplasms, Niclosamide, Phosphoproteins, Phosphorylation, Prostatic Neoplasms, Apoptosis, Cell Line, Tumor, Adaptor Proteins, Signal Transducing, Cell Proliferation, Wnt Proteins, beta Catenin, HEK293 Cells, Proteolysis, Wnt Signaling Pathway, Low Density Lipoprotein Receptor-Related Protein-6, Wnt3A Protein
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
