ArticleMolecular therapy : the journal of the American Society of Gene Therapy2022
A chemokine regulatory loop induces cholesterol synthesis in lung-colonizing triple-negative breast cancer cells to fuel metastatic growth.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2022. 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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Who cites it
24 citing papers in PubMed, 28 citations in OpenAlex.
- CXCL1 in triple‑negative breast cancer: Mechanisms, challenges, and therapeutic opportunities (Review).Oncology reports · 2026Review
- SREBP2 regulates CCDC25 expression and promotes tumor metastasis in Triple-Negative Breast Cancer.Oncogenesis · 2026Article
- Nicotinamide prevents anti-PD1 immune checkpoint inhibitor-associated early stages of cardiotoxicity.Science China. Life sciences · 2026Article
- Dynamic Metabolic States in TNBC: Orchestrating Spatiotemporal Adaptation and Therapy.Oncology research · 2026Review
- Nano-bioparticles: Fighting cancer with targeted nanotherapy.Open access government · 2026Article
- The chemokine network in triple-negative breast cancer: its role in immune microenvironment regulation, and prospects for targeted therapy.Frontiers in immunology · 2026Review
- Breast cancer cell coculture induces normal lung fibroblast transition to CAFs, promoting tumor cell dormancy and therapy resistance.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Prospective study of cesarean scar pregnancy associated with increased MCP-1 and cholesterol synthesis.Biomedical reports · 2025Article
- Adipocyte-derived IL6 and triple-negative breast cancer cell-derived CXCL1 co-activate STAT3/NF-κB pathway to mediate the crosstalk between adipocytes and triple-negative breast cancer cells.Cell death discovery · 2025Article
- Mechanisms of organotropism in breast cancer and predicting metastasis to distant organs using deep learning.Discover oncology · 2025Article
- Lung-specific metastasis: the coevolution of tumor cells and lung microenvironment.Molecular cancer · 2025Review
- Dual Inhibition of CDK4/6 and CDK7 Suppresses Triple-Negative Breast Cancer Progression via Epigenetic Modulation of SREBP1-Regulated Cholesterol Metabolism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Cholesterol: The driving force behind the remodeling of tumor microenvironment in colorectal cancer.Heliyon · 2024Review
- ZNF8 Orchestrates with Smad3 to Promote Lung Metastasis by Recruiting SMYD3 in Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Overcoming Resistance in Prostate Cancer Therapy Using a DZ-Simvastatin Conjugate.Molecular pharmaceutics · 2024Article
- Cholesterol metabolism in tumor microenvironment: cancer hallmarks and therapeutic opportunities.International journal of biological sciences · 2024Review
- Fibrin Stiffness Regulates Phenotypic Plasticity of Metastatic Breast Cancer Cells.Advanced healthcare materials · 2023Article
- Benzophenone-3 exposure alters composition of tumor infiltrating immune cells and increases lung seeding of 4T1 breast cancer cells.Advances in cancer biology - metastasis · 2023Article
- Involvement in Tumorigenesis and Clinical Significance of CXCL1 in Reproductive Cancers: Breast Cancer, Cervical Cancer, Endometrial Cancer, Ovarian Cancer and Prostate Cancer.International journal of molecular sciences · 2023Review
- CCR9 overexpression promotes T-ALL progression by enhancing cholesterol biosynthesis.Frontiers in pharmacology · 2023Article
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Authors and funding
16 authors at 3 institutions in 2 countries.
Funding
Abstract
Triple-negative breast cancer (TNBC) has a high propensity for organ-specific metastasis. However, the underlying mechanisms are not well understood. Here we show that the primary TNBC tumor-derived C-X-C motif chemokines 1/2/8 (CXCL1/2/8) stimulate lung-resident fibroblasts to produce the C-C motif chemokines 2/7 (CCL2/7), which, in turn, activate cholesterol synthesis in lung-colonizing TNBC cells and induce angiogenesis at lung metastatic sites. Inhibiting cholesterol synthesis in lung-colonizing breast tumor cells by pulmonary administration of simvastatin-carrying HER3-targeting nanoparticles reduces angiogenesis and growth of lung metastases in a syngeneic TNBC mouse model. Our findings reveal a novel, chemokine-regulated mechanism for the cholesterol synthesis pathway and a critical role of metastatic site-specific cholesterol synthesis in the pulmonary tropism of TNBC metastasis. The study has implications for the unresolved epidemiological observation that use of cholesterol-lowering drugs has no effect on breast cancer incidence but can unexpectedly reduce breast cancer mortality, suggesting interventions of cholesterol synthesis in lung metastases as an effective treatment to improve survival in individuals with TNBC.
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