ArticleDevelopmental cell2021
CLIP-170S is a microtubule +TIP variant that confers resistance to taxanes by impairing drug-target engagement.
Article in Developmental cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 12 citations in OpenAlex.
- Research Status and Hotspots of Anticancer Natural Products Based on the Patent Literature and Scientific Articles.Frontiers in pharmacology · 2022Pooled it
- Microtubule-Associated Proteins: From Dynamic Regulation of Microtubules to Cellular Architecture.Cells · 2026Review
- FOXJ1 mediates taxane resistance through regulation of microtubule dynamics.Nature communications · 2026Article
- Microtubule regulation in cancer cells.Frontiers in cell and developmental biology · 2025Article
- Computational analysis of treatment resistant cancer cells.Frontiers in cell and developmental biology · 2025Article
- CLIP170 enhancing FOSL1 expression via attenuating ubiquitin-mediated degradation of β-catenin drives renal cell carcinoma progression.Cellular and molecular life sciences : CMLS · 2024Article
- SEPT9_i1 and Septin Dynamics in Oncogenesis and Cancer Treatment.Biomolecules · 2024Review
- Co-expression pattern of SLC transporter genes associated with the immune landscape and clinical outcomes in gastric cancer.Journal of cellular and molecular medicine · 2023Article
- Bovine Colostrum Treatment of Specific Cancer Types: Current Evidence and Future Opportunities.Molecules (Basel, Switzerland) · 2022Review
- Tension of plus-end tracking protein Clip170 confers directionality and aggressiveness during breast cancer migration.Cell death & disease · 2022Article
Corrections and comments
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Authors and funding
16 authors at 6 institutions in 2 countries.
Funding
Abstract
Taxanes are widely used cancer chemotherapeutics. However, intrinsic resistance limits their efficacy without any actionable resistance mechanism. We have discovered a microtubule (MT) plus-end-binding CLIP-170 protein variant, hereafter CLIP-170S, which we found enriched in taxane-resistant cell lines and patient samples. CLIP-170S lacks the first Cap-Gly motif, forms longer comets, and impairs taxane access to its MT luminal binding site. CLIP-170S knockdown reversed taxane resistance in cells and xenografts, whereas its re-expression led to resistance, suggesting causation. Using a computational approach in conjunction with the connectivity map, we unexpectedly discovered that Imatinib was predicted to reverse CLIP-170S-mediated taxane resistance. Indeed, Imatinib treatment selectively depleted CLIP-170S, thus completely reversing taxane resistance. Other RTK inhibitors also depleted CLIP-170S, suggesting a class effect. Herein, we identify CLIP-170S as a clinically prevalent variant that confers taxane resistance, whereas the discovery of Imatinib as a CLIP-170S inhibitor provides novel therapeutic opportunities for future trials.
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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.