ArticleCell death & disease2019
Paclitaxel induces lymphatic endothelial cells autophagy to promote metastasis.
Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.
- Lymphatic immunomodulation using engineered drug delivery systems for cancer immunotherapy.Advanced drug delivery reviews · 2020Pooled it
- Integrated analyses of single-cell transcriptome and mendelian randomization reveal the role of lymphatic endothelial CD74 in the progression of atherosclerosis.Journal of geriatric cardiology : JGC · 2026Article
- Targeting the Vim-PGIHuman mutation · 2026Article
- Tertiary lymphoid structures are associated with lower axillary residual nodal burden in breast cancer patients after neoadjuvant chemotherapy.European journal of medical research · 2025Article
- Systemic Drugs Associated With Maculopathy.JAMA ophthalmology · 2025Article
- Unveiling the immunomodulatory dance: endothelial cells' function and their role in non-small cell lung cancer.Molecular cancer · 2025Review
- Cracking the code: predicting tumor microenvironment enabled chemoresistance with machine learning in the human tumoroid models.npj biomedical innovations · 2025Article
- Profibrotic VEGFR3-Dependent Lymphatic Vessel Growth in Autoimmune Valvular Carditis.Arteriosclerosis, thrombosis, and vascular biology · 2024Article
- The Crosstalk between Autophagy and Nrf2 Signaling in Cancer: from Biology to Clinical Applications.International journal of biological sciences · 2024Review
- Triple negative breast cancer: approved treatment options and their mechanisms of action.Journal of cancer research and clinical oncology · 2023Article
- An integrative review of nonobvious puzzles of cellular and molecular cardiooncology.Cellular & molecular biology letters · 2023Review
- Editorial: Autophagy modulation in cancer treatment utilizing nanomaterials and nanocarriers.Frontiers in oncology · 2023Article
- Mechanisms of cancer cell death induction by paclitaxel: an updated review.Apoptosis : an international journal on programmed cell death · 2022Review
- Elicitation of stem-like CD8Journal for immunotherapy of cancer · 2022Article
- Drug-Related Lymphedema: Mysteries, Mechanisms, and Potential Therapies.Frontiers in pharmacology · 2022Review
- Paclitaxel treatment enhances lymphatic metastasis of B16F10 melanoma cells via CCL21/CCR7 axis.International journal of biological sciences · 2022Article
- Autophagy and ncRNAs: Dangerous Liaisons in the Crosstalk between the Tumor and Its Microenvironment.Cancers · 2021Review
- Role of lymphatic endothelial cells in the tumor microenvironment-a narrative review of recent advances.Translational lung cancer research · 2021Review
- Oxidatively Modified LDL Suppresses Lymphangiogenesis via CD36 Signaling.Antioxidants (Basel, Switzerland) · 2021Article
- Seven Genes Associated With Lymphatic Metastasis in Thyroid Cancer That Is Linked to Tumor Immune Cell Infiltration.Frontiers in oncology · 2021Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cytotoxic therapy for breast cancer inhibits the growth of primary tumors, but promotes metastasis to the sentinel lymph nodes through the lymphatic system. However, the effect of first-line chemotherapy on the lymphatic endothelium has been poorly investigated. In this study, we determined that paclitaxel, the anti-cancer drug approved for the treatment of metastatic or locally advanced breast cancer, induces lymphatic endothelial cell (LEC) autophagy to increase metastases. While paclitaxel treatment was largely efficacious in inhibiting LEC adhesion, it had no effect on cell survival. Paclitaxel inhibited LEC migration and branch point formation by inducing an autophagy mechanism independent of Akt phosphorylation. In vivo, paclitaxel mediated a higher permeability of lymphatic endothelium to tumor cells and this effect was reversed by chloroquine, an autophagy-lysosome inhibitor. Despite a strong effect on reducing tumor size, paclitaxel significantly increased metastasis to the sentinel lymph nodes. This effect was restricted to a lymphatic dissemination, as chemotherapy did not affect the blood endothelium. Taken together, our findings suggest that the lymphatic system resists to chemotherapy through an autophagy mechanism to promote malignant progression and metastatic lesions. This study paves the way for new combinative therapies aimed at reducing the number of metastases.
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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.