ArticleCellular signalling2014
Rottlerin induces Wnt co-receptor LRP6 degradation and suppresses both Wnt/β-catenin and mTORC1 signaling in prostate and breast cancer cells.
Article in Cellular signalling, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- Phytochemicals regulate cancer metabolism through modulation of the AMPK/PGC-1α signaling pathway.BMC cancer · 2024Pooled it
- Stemness regulation in prostate cancer: prostate cancer stem cells and targeted therapy.Annals of medicine · 2025Review
- Role of the Wnt signaling pathway in the complex microenvironment of breast cancer and prospects for therapeutic potential (Review).International journal of oncology · 2025Review
- Research Progress on the Role of Zinc Finger Protein in Colorectal Cancer.Cancer reports (Hoboken, N.J.) · 2025Review
- Multifaceted effects of LRP6 in cancer: exploring tumor development, immune modulation and targeted therapies.Medical oncology (Northwood, London, England) · 2024Review
- LowCancers · 2024Article
- Molecular targets and therapeutic strategies for triple-negative breast cancer.Molecular biology reports · 2023Review
- Rottlerin suppresses lipid accumulation by inhibiting de novo lipogenesis and adipogenesis via LRP6/mTOR/SREBP1C in 3T3-L1 adipocytes.Food science and biotechnology · 2023Article
- Screening and Identification of ssDNA Aptamers for Low-Density Lipoprotein (LDL) Receptor-Related Protein 6.Molecules (Basel, Switzerland) · 2023Article
- The Relationship between LRP6 and Wnt/β-Catenin Pathway in Colorectal and Esophageal Cancer.Life (Basel, Switzerland) · 2023Article
- Wnt/β-catenin signaling pathway in the tumor progression of adrenocortical carcinoma.Frontiers in endocrinology · 2023Review
- Countering Triple Negative Breast Cancer via Impeding Wnt/β-Catenin Signaling, a Phytotherapeutic Approach.Plants (Basel, Switzerland) · 2022Review
- Predicting Novel Drug Candidates for Pancreatic Neuroendocrine Tumors via Gene Signature Comparison and Connectivity Mapping.Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract · 2022Article
- Herbal Ingredients in the Prevention of Breast Cancer: Comprehensive Review of Potential Molecular Targets and Role of Natural Products.Oxidative medicine and cellular longevity · 2022Review
- A 5`-tRNA Derived Fragment NamedtiRNA-Val-CAC-001 Works as a Suppressor in Gastric Cancer.Cancer management and research · 2022Article
- Transmembrane protein 97 exhibits oncogenic properties via enhancing LRP6-mediated Wnt signaling in breast cancer.Cell death & disease · 2021Article
- Targeting Wnt signaling pathway by polyphenols: implication for aging and age-related diseases.Biogerontology · 2021Review
- Wnt/β-catenin signaling in cancers and targeted therapies.Signal transduction and targeted therapy · 2021Review
- LRP6 as a biomarker of poor prognosis of breast cancer.Gland surgery · 2021Article
- Rottlerin, BDNF, and the impairment of inhibitory avoidance memory.Psychopharmacology · 2021Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 2 countries.
Funding
Abstract
Activation of Wnt/β-catenin signaling can result in up-regulation of mTORC1 signaling in cancer cells. The low density lipoprotein receptor-related protein-6 (LRP6) is an essential Wnt co-receptor for Wnt/β-catenin signaling. We found that rottlerin, a natural plant polyphenol, suppressed LRP6 expression and phosphorylation, and inhibited Wnt/β-catenin signaling in HEK293 cells. Furthermore, the inhibitory effects of rottlerin on LRP6 expression/phosphorylation and Wnt/β-catenin signaling were confirmed in human prostate cancer PC-3 and DU145 cells and breast cancer MDA-MB-231 and T-47D cells. Mechanistically, rottlerin promoted LRP6 degradation, but had no effects on LRP6 transcriptional activity. In addition, rottlerin-mediated LRP6 down-regulation was unrelated to activation of 5'-AMP-activated protein kinase (AMPK). Importantly, we also found that rottlerin inhibited mTORC1 signaling in prostate and breast cancer cells. Finally, we demonstrated that rottlerin was able to suppress the expression of cyclin D1 and survivin, two targets of both Wnt/β-catenin and mTORC1 signaling, in prostate and breast cancer cells, and displayed remarkable anticancer activity with IC(50) values between 0.7 and 1.7 μM for prostate cancer PC-3 and DU145 cells and breast cancer MDA-MB-231 and T-47D cells. The IC(50) values are comparable to those shown to suppress the activities of Wnt/β-catenin and mTORC1 signaling in prostate and breast cancer cells. Our data indicate that rottlerin is a novel LRP6 inhibitor and suppresses both Wnt/β-catenin and mTORC1 signaling in prostate and breast cancer cells, and that LRP6 represents a potential therapeutic target for cancers.
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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.