ArticleJournal of experimental & clinical cancer research : CR2019
Discovery of a natural small-molecule compound that suppresses tumor EMT, stemness and metastasis by inhibiting TGFβ/BMP signaling in triple-negative breast cancer.
Article in Journal of experimental & clinical cancer research : CR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
24 citing papers in PubMed, 48 citations in OpenAlex.
- Evaluation of Itraconazole as a repurposed small molecule inhibitor of EMT in breast cancer: a molecular docking and dynamics study.Journal of molecular modeling · 2026Article
- Therapy as a State-Generator: Dynamic Phenotypic Landscapes and Adaptive Stress Circuits in Chemotherapy Resistance of Breast Cancer.Antioxidants (Basel, Switzerland) · 2026Review
- Disruption of HSPA8-GEMIN5 interaction suppresses colorectal cancer by impaired splicing-translation coupling-mediated proteostasis imbalance.Journal of experimental & clinical cancer research : CR · 2026Article
- The bibliometric and visualized analysis on cancer stem cells in the early 21st century.International journal of surgery (London, England) · 2026Review
- Comprehensive pan-cancer analysis of USP35 and validation of its role in gastric cancer.Human genomics · 2025Article
- Translational drugs targeting cancer stem cells in triple-negative breast cancer.Molecular therapy. Oncology · 2025Review
- POC1A induces epithelial-mesenchymal transition to promote growth and metastasis through the STAT3 signaling pathway in triple-negative breast cancer.Molecular medicine (Cambridge, Mass.) · 2025Article
- A novel FGFR1 inhibitor CYY292 suppresses tumor progression, invasion, and metastasis of glioblastoma by inhibiting the Akt/GSK3β/snail signaling axis.Genes & diseases · 2024Article
- Upregulated bone morphogenetic protein 8A (BMP8A) in triple negative breast cancer (TNBC) and its involvement in the bone metastasis.Frontiers in cell and developmental biology · 2024Article
- Signaling pathways governing the maintenance of breast cancer stem cells and their therapeutic implications.Frontiers in cell and developmental biology · 2023Review
- Metastasis prevention: targeting causes and roots.Clinical & experimental metastasis · 2022Review
- Structural Optimization and Improving Antitumor Potential of Moreollic Acid fromMolecules (Basel, Switzerland) · 2022Article
- Potential bioactive compounds and mechanisms ofFrontiers in aging neuroscience · 2022Article
- Heterogeneity of BCSCs contributes to the metastatic organotropism of breast cancer.Journal of experimental & clinical cancer research : CR · 2021Review
- Inhibiting roles of FOXA2 in liver cancer cell migration and invasion by transcriptionally suppressing microRNA-103a-3p and activating the GREM2/LATS2/YAP axis.Cytotechnology · 2021Article
- Deciphering molecular mechanisms of metastasis: novel insights into targets and therapeutics.Cellular oncology (Dordrecht, Netherlands) · 2021Review
- Paving the way for small-molecule drug discovery.American journal of translational research · 2021Review
- Basic approaches, challenges and opportunities for the discovery of small molecule anti-tumor drugs.American journal of cancer research · 2021Review
- Long non‑coding RNA NEAT1 promotes ovarian cancer cell invasion and migration by interacting with miR‑1321 and regulating tight junction protein 3 expression.Molecular medicine reports · 2020Article
- Annurca apple polyphenol extract promotes mesenchymal-to-epithelial transition and inhibits migration in triple-negative breast cancer cells through ROS/JNK signaling.Scientific reports · 2020Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundThe transforming growth factor β (TGFβ) and bone morphogenetic protein (BMP) signaling pathways are both constitutively activated in triple-negative breast cancer (TNBC). We are interested in isolating the naturally-derived small-molecule inhibitor that could simultaneously targeting TGFβ/BMP pathways and further studying its anti-proliferative/-metastatic effects as well as the underlying mechanisms in multiple tumor models.
methodsMultiple in vitro cell-based assays are used to examine the compound's inhibitory efficacy on TNBC cell growth, stemness, epithelial-mesenchymal transition (EMT), invasion and migration by targeting TGFβ/BMP signaling pathways. Transgenic breast cancer mouse model (MMTV-PyMT), subcutaneous xenograft and bone metastasis models are used to examine ZL170's effects on TNBC growth and metastasis potentials in vivo.
resultsZL170 dose-dependently inhibits cell proliferation, EMT, stemness, invasion and migration in vitro via specifically targeting canonical TGFβ/BMP-SMADs pathways in TNBC cells. The compound significantly hinders osteolytic bone metastasis and xenograft tumor growth without inflicting toxicity on vital organs of tumor-bearing nude mice. ZL170 strongly inhibits primary tumor growth and lung metastases in MMTV-PyMT transgenic mice. ZL170-treated tumors exhibit impaired TGFβ/BMP signaling pathways in both epithelial and stromal compartments, thereby creating a suppressive tumor microenvironment characterized by reduced extracellular matrix deposition and decreased infiltration of stromal cells.
conclusionsZL170 inhibits tumor EMT, stemness and metastasis and could be further developed as a potent anti-metastatic agent used in combination with cytotoxic drugs for treatment of TNBC and other advanced metastatic cancers.
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Registered trials
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.