ArticlePloS one2020
An iron-dependent metabolic vulnerability underlies VPS34-dependence in RKO cancer cells.
Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 12 citations in OpenAlex.
- Effect of ART1 on the efficacy of oxaliplatin in colorectal cancer under high-cholesterol conditions.Histology and histopathology · 2026Article
- VPS34 in Autophagy, Cancer, and Cancer Therapy.Cells · 2026Review
- PIK-III-Mediated Elevation of Thiamine Re-Sensitises Renal Cell Carcinoma to Cuproptosis via Activating PDHA1.Cell proliferation · 2026Article
- Signaling mechanisms and cis -regulatory control of Samd14 in erythroid regeneration.Current opinion in hematology · 2025Review
- Regulatory Mechanisms Governing the Autophagy-Initiating VPS34 Complex and Its inhibitors.Biomolecules & therapeutics · 2024Review
- Targeting PI3K family with small-molecule inhibitors in cancer therapy: current clinical status and future directions.Molecular cancer · 2024Review
- Targeting Class I-II-III PI3Ks in Cancer Therapy: Recent Advances in Tumor Biology and Preclinical Research.Cancers · 2023Review
- Targeting phosphoinositide signaling in cancer: relevant techniques to study lipids and novel avenues for therapeutic intervention.Frontiers in cell and developmental biology · 2023Article
- Inhibiting Cytoprotective Autophagy in Cancer Therapy: An Update on Pharmacological Small-Molecule Compounds.Frontiers in pharmacology · 2022Review
- The Role of Phosphatidylinositol 3-Kinase Catalytic Subunit Type 3 in the Pathogenesis of Human Cancer.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
22 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
VPS34 is a key regulator of endomembrane dynamics and cargo trafficking, and is essential in cultured cell lines and in mice. To better characterize the role of VPS34 in cell growth, we performed unbiased cell line profiling studies with the selective VPS34 inhibitor PIK-III and identified RKO as a VPS34-dependent cellular model. Pooled CRISPR screen in the presence of PIK-III revealed endolysosomal genes as genetic suppressors. Dissecting VPS34-dependent alterations with transcriptional profiling, we found the induction of hypoxia response and cholesterol biosynthesis as key signatures. Mechanistically, acute VPS34 inhibition enhanced lysosomal degradation of transferrin and low-density lipoprotein receptors leading to impaired iron and cholesterol uptake. Excess soluble iron, but not cholesterol, was sufficient to partially rescue the effects of VPS34 inhibition on mitochondrial respiration and cell growth, indicating that iron limitation is the primary driver of VPS34-dependency in RKO cells. Loss of RAB7A, an endolysosomal marker and top suppressor in our genetic screen, blocked transferrin receptor degradation, restored iron homeostasis and reversed the growth defect as well as metabolic alterations due to VPS34 inhibition. Altogether, our findings suggest that impaired iron mobilization via the VPS34-RAB7A axis drive VPS34-dependence in certain cancer cells.
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