ArticleScientific reports2015
Protein receptor-independent plasma membrane remodeling by HAMLET: a tumoricidal protein-lipid complex.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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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
16 citing papers in PubMed, 30 citations in OpenAlex.
- Clinical and molecular response to alpha1-oleate treatment in patients with bladder cancer.Cancer medicine · 2024Trial
- Bladder cancer therapy using a conformationally fluid tumoricidal peptide complex.Nature communications · 2021Trial
- Bacterial protein-oleate complexes induce ferroptosis-like cell death in colorectal cancer cells by disrupting cell membranes and inhibiting the β-catenin-GPX4 axis.Cell death discovery · 2026Article
- Rapid ER remodeling induced by a peptide-lipid complex in dying tumor cells.Life science alliance · 2025Article
- Fabrication of α-lactalbumin-coated chamomile nano-emulsion for their synergistic anticancer and anti-inflammatory applications.Medical oncology (Northwood, London, England) · 2025Article
- Cholesterol-Dependent Membrane Deformation by Metastable Viral Capsids Facilitates Entry.ACS infectious diseases · 2024Article
- Cholesterol-Dependent Membrane Deformation by Metastable Viral Capsids Facilitates Entry.bioRxiv : the preprint server for biology · 2024Article
- Augmenting apoptosis-mediated anticancer activity of lactoperoxidase and lactoferrin by nanocombination with copper and iron hybrid nanometals.Scientific reports · 2022Article
- The Molten Globule State of a Globular Protein in a Cell Is More or Less Frequent Case Rather than an Exception.Molecules (Basel, Switzerland) · 2022Review
- Article
- Identification and in silico characterization of structural and functional impacts of genetic variants in milk protein genes in the Zebu breeds Guzerat and Gyr.Tropical animal health and production · 2021Article
- A scientific journey from discovery to validation of efficacy in cancer patients: HAMLET and alpha1-oleate.Molecular & cellular oncology · 2021Article
- α-Lactalbumin, Amazing Calcium-Binding Protein.Biomolecules · 2020Review
- BAMLET kills chemotherapy-resistant mesothelioma cells, holding oleic acid in an activated cytotoxic state.PloS one · 2018Article
- Efficiency of novel nanocombinations of bovine milk proteins (lactoperoxidase and lactoferrin) for combating different human cancer cell lines.Scientific reports · 2017Article
- Protein-dependent Membrane Interaction of A Partially Disordered Protein Complex with Oleic Acid: Implications for Cancer Lipidomics.Scientific reports · 2016Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 4 countries.
Funding
Abstract
A central tenet of signal transduction in eukaryotic cells is that extra-cellular ligands activate specific cell surface receptors, which orchestrate downstream responses. This ''protein-centric" view is increasingly challenged by evidence for the involvement of specialized membrane domains in signal transduction. Here, we propose that membrane perturbation may serve as an alternative mechanism to activate a conserved cell-death program in cancer cells. This view emerges from the extraordinary manner in which HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells) kills a wide range of tumor cells in vitro and demonstrates therapeutic efficacy and selectivity in cancer models and clinical studies. We identify a ''receptor independent" transformation of vesicular motifs in model membranes, which is paralleled by gross remodeling of tumor cell membranes. Furthermore, we find that HAMLET accumulates within these de novo membrane conformations and define membrane blebs as cellular compartments for direct interactions of HAMLET with essential target proteins such as the Ras family of GTPases. Finally, we demonstrate lower sensitivity of healthy cell membranes to HAMLET challenge. These features suggest that HAMLET-induced curvature-dependent membrane conformations serve as surrogate receptors for initiating signal transduction cascades, ultimately leading to cell death.
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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.