ArticleMolecular and cellular biology2013
Fendiline inhibits K-Ras plasma membrane localization and blocks K-Ras signal transmission.
Article in Molecular and cellular biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 112 citations in OpenAlex.
- Targeting KRAS mutations: orchestrating cancer evolution and therapeutic challenges.Signal transduction and targeted therapy · 2025Review
- RAS-membrane interaction and oligomerization: there is more than meets the eye.Biochemical Society transactions · 2025Review
- MTMR regulates KRAS function by controlling plasma membrane levels of phospholipids.The Journal of cell biology · 2025Article
- AGTR1 potentiates the chemotherapeutic efficacy of cisplatin in esophageal carcinoma through elevation of intracellular CaInternational journal of oncology · 2025Article
- KRAS Mutation Subtypes and Their Association with Other Driver Mutations in Oncogenic Pathways.Cells · 2024Review
- Leveraging altered lipid metabolism in treating B cell malignancies.Progress in lipid research · 2024Review
- A new ferrocene derivative blocks K-Ras localization and function by oxidative modification at His95.Life science alliance · 2023Article
- RAS GTPases and Interleaflet Coupling in the Plasma Membrane.Cold Spring Harbor perspectives in biology · 2023Review
- Sphingomyelin metabolism underlies Ras excitability for efficient cell migration and chemotaxis.Cell structure and function · 2023Article
- Article
- RAS nanoclusters are cell surface transducers that convert extracellular stimuli to intracellular signalling.FEBS letters · 2023Review
- NRas activity is regulated by dynamic interactions with nanoscale signaling clusters at the plasma membrane.iScience · 2022Article
- Phosphatidylserine clustering by the Ebola virus matrix protein is a critical step in viral budding.EMBO reports · 2022Article
- Calcium channel blockers potentiate gemcitabine chemotherapy in pancreatic cancer.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Targeting Ion Channels for Cancer Treatment: Current Progress and Future Challenges.Reviews of physiology, biochemistry and pharmacology · 2022Review
- Past and Future Strategies to Inhibit Membrane Localization of the KRAS Oncogene.International journal of molecular sciences · 2021Review
- Lipid Profiles of RAS Nanoclusters Regulate RAS Function.Biomolecules · 2021Review
- Efficacy of a Three Drug-Based Therapy for Neuroblastoma in Mice.International journal of molecular sciences · 2021Article
- Scaffold repurposing of fendiline: Identification of potent KRAS plasma membrane localization inhibitors.European journal of medicinal chemistry · 2021Article
- RAS Nanoclusters: Dynamic Signaling Platforms Amenable to Therapeutic Intervention.Biomolecules · 2021Review
8 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Ras proteins regulate signaling pathways important for cell growth, differentiation, and survival. Oncogenic mutant Ras proteins are commonly expressed in human tumors, with mutations of the K-Ras isoform being most prevalent. To be active, K-Ras must undergo posttranslational processing and associate with the plasma membrane. We therefore devised a high-content screening assay to search for inhibitors of K-Ras plasma membrane association. Using this assay, we identified fendiline, an L-type calcium channel blocker, as a specific inhibitor of K-Ras plasma membrane targeting with no detectable effect on the localization of H- and N-Ras. Other classes of L-type calcium channel blockers did not mislocalize K-Ras, suggesting a mechanism that is unrelated to calcium channel blockade. Fendiline did not inhibit K-Ras posttranslational processing but significantly reduced nanoclustering of K-Ras and redistributed K-Ras from the plasma membrane to the endoplasmic reticulum (ER), Golgi apparatus, endosomes, and cytosol. Fendiline significantly inhibited signaling downstream of constitutively active K-Ras and endogenous K-Ras signaling in cells transformed by oncogenic H-Ras. Consistent with these effects, fendiline blocked the proliferation of pancreatic, colon, lung, and endometrial cancer cell lines expressing oncogenic mutant K-Ras. Taken together, these results suggest that inhibitors of K-Ras plasma membrane localization may have utility as novel K-Ras-specific anticancer therapeutics.
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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.