ArticleMolecular cancer therapeutics2013
Tumor-initiating cells and FZD8 play a major role in drug resistance in triple-negative breast cancer.
Article in Molecular cancer therapeutics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 65 citations in OpenAlex.
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- Unraveling the influence of α-mangostin on MDA-MB-231 cell line via WNT/β-catenin signaling pathway:Frontiers in pharmacology · 2025Article
- Frizzled receptors (FZDs) in Wnt signaling: potential therapeutic targets for human cancers.Acta pharmacologica Sinica · 2024Review
- The regulation of microRNAs on chemoresistance in triple-negative breast cancer: a recent update.Epigenomics · 2024Review
- Expression pattern, prognostic value and potential microRNA silencing of FZD8 in breast cancer.Oncology letters · 2023Article
- Yin Yang 1 promotes the neuroendocrine differentiation of prostate cancer cells via the non-canonical WNT pathway (FYN/STAT3).Clinical and translational medicine · 2023Article
- Identification of vascular cues contributing to cancer cell stemness and function.Angiogenesis · 2022Article
- Diallyl disulfide and diallyl trisulfide in garlic as novel therapeutic agents to overcome drug resistance in breast cancer.Journal of pharmaceutical analysis · 2022Review
- Small Molecule Compounds of Natural Origin Target Cellular Receptors to Inhibit Cancer Development and Progression.International journal of molecular sciences · 2022Review
- Molecular Mechanisms, Biomarkers and Emerging Therapies for Chemotherapy Resistant TNBC.International journal of molecular sciences · 2022Review
- Role of microRNA/lncRNA Intertwined With the Wnt/β-Catenin Axis in Regulating the Pathogenesis of Triple-Negative Breast Cancer.Frontiers in pharmacology · 2022Review
- lncRNA GHET1 Promotes the Progression of Triple-Negative Breast CancerComputational and mathematical methods in medicine · 2022Article
- A novel 12-gene signature as independent prognostic model in stage IA and IB lung squamous cell carcinoma patients.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2021Article
- Breast Ultrasound Microvascular Imaging and Radiogenomics.Korean journal of radiology · 2021Review
- Frizzled Receptors in Tumors, Focusing on Signaling, Roles, Modulation Mechanisms, and Targeted Therapies.Oncology research · 2021Review
- Expression and prognostic impact of FZDs in pancreatic adenocarcinoma.BMC gastroenterology · 2021Article
- Non-Coding RNA and Frizzled Receptors in Cancer.Frontiers in molecular biosciences · 2021Review
- A Computational Framework to Identify Biomarkers for Glioma Recurrence and Potential Drugs Targeting Them.Frontiers in genetics · 2021Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Triple-negative breast cancer (TNBC) studies have shown that neoadjuvant chemotherapy before surgery was effective in the minority of women, whereas the majority who had residual tumor had a relatively poor outcome. To identify the mechanism by which residual cancer cells survive chemotherapy, we initially conducted gene expression profiling using the CRL2335 TNBC cell line derived from a squamous breast carcinoma before and after treatment with cisplatin plus TRAIL. We found a significant increase in the expression of FZD8, one of Wnt receptors, and its downstream targets LEF1 and TCF in residual CRL2335 tumor cells after treatment with cisplatin plus TRAIL. Increased FZD8 levels were further confirmed in other TNBC cell lines. Inhibition of FZD8 by siRNA in CRL2335 cells in the presence of cisplatin plus TRAIL reduced β-catenin and survivin levels and increased apoptosis compared with scrambled siRNA-treated cells. In vivo data show that cisplatin plus TRAIL treatment significantly reduces tumor volume in NOD/SCID mice. However, we found that cisplatin plus TRAIL treatment predominantly eliminated non-tumor-initiating cells, as shown by whole-body fluorescent imaging of mice injected with mammosphere-forming CRL2335 cells stably transfected with DsRed. This led to TIC enrichment in residual tumors, as confirmed by immunostaining for TIC markers. Moreover, an increase in FZD8 expression was observed in residual tumors treated with cisplatin and TRAIL. Taken together, our findings suggest that FZD8-mediated Wnt signaling may play a major role in mediating resistance to chemotherapy, making it a potential target to enhance chemotherapeutic efficacy in patients with TNBCs.
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