ArticleLife science alliance2019
Targeting plasma membrane phosphatidylserine content to inhibit oncogenic KRAS function.
Article in Life science alliance, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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The trial behind it
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Who cites it
32 citing papers in PubMed, 44 citations in OpenAlex.
- KRAS G12C and KRAS G12D respond to lipid metabolism in an allele-specific manner.Journal of lipid research · 2026Article
- Glycosphingolipids regulate phosphatidylserine transport machinery that operates at ER-PM contact sites.Nature communications · 2026Article
- Statins in Membrane Lipid Therapy: Mechanistic Promise Versus Clinical Reality.International journal of molecular sciences · 2026Article
- Phosphatidylinositol 4-kinase α suppresses glioblastoma progression by inactivating YAP and PI3K/Akt signaling.The Journal of biological chemistry · 2026Article
- Dynamic Shifts in ER-Plasma Membrane Junctions Signaling Define Pro-Metastatic N-Glycosylation and Predict Prostate Cancer Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Phosphatidylserine transporters ORP5 and ORP8 control cholesterol trafficking from the plasma membrane to the endoplasmic reticulum.Journal of lipid research · 2026Article
- MTMR regulates KRAS function by controlling plasma membrane levels of phospholipids.The Journal of cell biology · 2025Article
- Dys-regulated phosphatidylserine externalization as a cell intrinsic immune escape mechanism in cancer.Cell communication and signaling : CCS · 2025Review
- Targeting membrane contact sites to mediate lipid dynamics: innovative cancer therapies.Cell communication and signaling : CCS · 2025Review
- KRas4b-Calmodulin Interaction with Membrane Surfaces: Role of Headgroup, Acyl Chain, and Electrostatics.Biochemistry · 2024Article
- Phosphatidylserine regulates plasma membrane repair through tetraspanin-enriched macrodomains.The Journal of cell biology · 2024Article
- A new ferrocene derivative blocks K-Ras localization and function by oxidative modification at His95.Life science alliance · 2023Article
- The phospholipid transporter PITPNC1 links KRAS to MYC to prevent autophagy in lung and pancreatic cancer.Molecular cancer · 2023Article
- RAS nanoclusters are cell surface transducers that convert extracellular stimuli to intracellular signalling.FEBS letters · 2023Review
- Glycolysis regulates KRAS plasma membrane localization and function through defined glycosphingolipids.Nature communications · 2023Article
- Targeting phosphoinositide signaling in cancer: relevant techniques to study lipids and novel avenues for therapeutic intervention.Frontiers in cell and developmental biology · 2023Article
- Nanoscopic Spatial Association between Ras and Phosphatidylserine on the Cell Membrane Studied with Multicolor Super Resolution Microscopy.Biomolecules · 2022Article
- Phospholipid Membrane Transport and Associated Diseases.Biomedicines · 2022Review
- 3,4,5-Trimethoxybenzoate of Catechin, an Anticarcinogenic Semisynthetic Catechin, Modulates the Physical Properties of Anionic Phospholipid Membranes.Molecules (Basel, Switzerland) · 2022Article
- Intracellular Cholesterol Synthesis and Transport.Frontiers in cell and developmental biology · 2022Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The small GTPase KRAS, which is frequently mutated in human cancers, must be localized to the plasma membrane (PM) for biological activity. We recently showed that the KRAS C-terminal membrane anchor exhibits exquisite lipid-binding specificity for select species of phosphatidylserine (PtdSer). We, therefore, investigated whether reducing PM PtdSer content is sufficient to abrogate KRAS oncogenesis. Oxysterol-related binding proteins ORP5 and ORP8 exchange PtdSer synthesized in the ER for phosphatidyl-4-phosphate synthesized in the PM. We show that depletion of ORP5 or ORP8 reduced PM PtdSer levels, resulting in extensive mislocalization of KRAS from the PM. Concordantly, ORP5 or ORP8 depletion significantly reduced proliferation and anchorage-independent growth of multiple KRAS-dependent cancer cell lines, and attenuated KRAS signaling in vivo. Similarly, functionally inhibiting ORP5 and ORP8 by inhibiting PI4KIIIα-mediated synthesis of phosphatidyl-4-phosphate at the PM selectively inhibited the growth of KRAS-dependent cancer cell lines over normal cells. Inhibiting KRAS function through regulating PM lipid PtdSer content may represent a viable strategy for KRAS-driven cancers.
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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.