ArticleOncotarget2017
Rapalogs can promote cancer cell stemness in vitro in a Galectin-1 and H-ras-dependent manner.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 23 citations in OpenAlex.
- Article
- Nuclear Galectin-1 Drives Cancer Progression throughInternational journal of biological sciences · 2026Article
- The role of immune checkpoints in modulating cancer stem cells anti-tumor immune responses: implications and perspectives in cancer therapy.Journal of experimental & clinical cancer research : CR · 2025Review
- Identification of an H-Ras nanocluster disrupting peptide.Communications biology · 2024Article
- RAS G-domains allosterically contribute to the recognition of lipid headgroups and acyl chains.The Journal of cell biology · 2024Article
- Dysregulation of cellular membrane homeostasis as a crucial modulator of cancer risk.The FEBS journal · 2024Review
- Vitexin suppresses the proliferation, angiogenesis and stemness of endometrial cancer through the PI3K/AKT pathway.Pharmaceutical biology · 2023Article
- RAS GTPases and Interleaflet Coupling in the Plasma Membrane.Cold Spring Harbor perspectives in biology · 2023Review
- RAS nanoclusters are cell surface transducers that convert extracellular stimuli to intracellular signalling.FEBS letters · 2023Review
- Tumour Stem Cells in Breast Cancer.International journal of molecular sciences · 2022Review
- Lipid Profiles of RAS Nanoclusters Regulate RAS Function.Biomolecules · 2021Review
- Promotion of cancer cell stemness by Ras.Biochemical Society transactions · 2021Review
- FLIM-FRET Analysis of Ras Nanoclustering and Membrane-Anchorage.Methods in molecular biology (Clifton, N.J.) · 2021Article
- RAS Nanoclusters Selectively Sort Distinct Lipid Headgroups and Acyl Chains.Frontiers in molecular biosciences · 2021Review
- Review
- Article
- The Breast Cancer Stem Cells Traits and Drug Resistance.Frontiers in pharmacology · 2020Review
- Concepts and advances in cancer therapeutic vulnerabilities in RAS membrane targeting.Seminars in cancer biology · 2019Review
- Functional link between plasma membrane spatiotemporal dynamics, cancer biology, and dietary membrane-altering agents.Cancer metastasis reviews · 2018Review
- Oncogenic Ras Isoforms Signaling Specificity at the Membrane.Cancer research · 2018Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Currently several combination treatments of mTor- and Ras-pathway inhibitors are being tested in cancer therapy. While multiple feedback loops render these central signaling pathways robust, they complicate drug targeting.Here, we describe a novel H-ras specific feedback, which leads to an inadvertent rapalog induced activation of tumorigenicity in Ras transformed cells. We find that rapalogs specifically increase nanoscale clustering (nanoclustering) of oncogenic H-ras but not K-ras on the plasma membrane. This increases H-ras signaling output, promotes mammosphere numbers in a H-ras-dependent manner and tumor growth in ovo. Surprisingly, also other FKBP12 binders, but not mTor-inhibitors, robustly decrease FKBP12 levels after prolonged (>2 days) exposure. This leads to an upregulation of the nanocluster scaffold galectin-1 (Gal-1), which is responsible for the rapamycin-induced increase in H-ras nanoclustering and signaling output. We provide evidence that Gal-1 promotes stemness features in tumorigenic cells. Therefore, it may be necessary to block inadvertent induction of stemness traits in H-ras transformed cells by specific Gal-1 inhibitors that abrogate its effect on H-ras nanocluster. On a more general level, our findings may add an important mechanistic explanation to the pleiotropic physiological effects that are observed with rapalogs.
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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.