ArticleCancer science2017
Mitochondrial uncoupler exerts a synthetic lethal effect against β-catenin mutant tumor cells.
Article in Cancer science, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 22 citations in OpenAlex.
- Regulatory effect of Wnt signaling on mitochondria in cancer: from mechanism to therapy.Apoptosis : an international journal on programmed cell death · 2025Review
- Reduced Expression of UPRmt Proteins HSP10, HSP60, HTRA2, OMA1, SPG7, and YME1L Is Associated with Accelerated Heart Failure in Humans.Biomedicines · 2025Article
- Identification of osteoarthritis-associated chondrocyte subpopulations and key gene-regulating drugs based on multi-omics analysis.Scientific reports · 2025Article
- A novel role for nonactin: interfering with G-quadruplex in RET-driven medullary thyroid cancer.BMC cancer · 2024Article
- Multifaceted roles of aerobic glycolysis and oxidative phosphorylation in hepatocellular carcinoma.PeerJ · 2023Review
- Identification of the polyether ionophore lenoremycin through a new screening strategy for targeting cancer stem cells.The Journal of antibiotics · 2022Article
- Natural products targeting cancer cell dependency.The Journal of antibiotics · 2021Review
- Crosstalk of the Wnt/β-Catenin Signaling Pathway in the Induction of Apoptosis on Cancer Cells.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Mitochondrial Metabolism, Contact Sites and Cellular Calcium Signaling: Implications for Tumorigenesis.Cancers · 2020Review
- The influence of mitochondrial-directed regulation of Wnt signaling on tumorigenesis.Gastroenterology report · 2020Review
- Inhibiting eukaryotic ribosome biogenesis.BMC biology · 2019Article
- MiR-1180 from bone marrow MSCs promotes cell proliferation and glycolysis in ovarian cancer cells via SFRP1/Wnt pathway.Cancer cell international · 2019Article
- Identification of DK419, a potent inhibitor of Wnt/β-catenin signaling and colorectal cancer growth.Bioorganic & medicinal chemistry · 2018Article
- Mitochondrial uncoupler exerts a synthetic lethal effect against β-catenin mutant tumor cells.Cancer science · 2017Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The wingless/int-1 (Wnt) signal transduction pathway plays a central role in cell proliferation, survival, differentiation and apoptosis. When β-catenin: a component of the Wnt pathway, is mutated into an active form, cell growth signaling is hyperactive and drives oncogenesis. As β-catenin is mutated in a wide variety of tumors, including up to 10% of all sporadic colon carcinomas and 20% of hepatocellular carcinomas, it has been considered a promising target for therapeutic interventions. Therefore, we screened an in-house natural product library for compounds that exhibited synthetic lethality towards β-catenin mutations and isolated nonactin, an antibiotic mitochondrial uncoupler, as a hit compound. Nonactin, as well as other mitochondrial uncouplers, induced apoptosis selectively in β-catenin mutated tumor cells. Significant tumor regression was observed in the β-catenin mutant HCT 116 xenograft model, but not in the β-catenin wild type A375 xenograft model, in response to daily administration of nonactin in vivo. Furthermore, we found that expression of an active mutant form of β-catenin induced a decrease in the glycolysis rate. Taken together, our results demonstrate that tumor cells with mutated β-catenin depend on mitochondrial oxidative phosphorylation for survival. Therefore, they undergo apoptosis in response to mitochondrial dysfunction following the addition of mitochondrial uncouplers, such as nonactin. These results suggest that targeting mitochondria is a potential chemotherapeutic strategy for tumor cells that harbor β-catenin mutations.
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