ArticleProceedings of the National Academy of Sciences of the United States of America2015
Discovery and functional characterization of a neomorphic PTEN mutation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
33 citing papers in PubMed, 51 citations in OpenAlex.
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- Deep learning prioritizes cancer mutations that alter protein nucleocytoplasmic shuttling to drive tumorigenesis.Nature communications · 2025Article
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- Mass spectrometry-intensive top-down proteomics: an update on technology advancements and biomedical applications.Analytical methods : advancing methods and applications · 2024Review
- Investigating the effects of PTEN mutations on cGAS-STING pathway in glioblastoma tumours.Journal of neuro-oncology · 2024Article
- Capillary Zone Electrophoresis-Tandem Mass Spectrometry for Top-Down Proteomics of Mouse Brain Integral Membrane Proteins.Analytical chemistry · 2023Article
- Two cooperative binding sites sensitize PI(4,5)PScience advances · 2022Article
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- Anoikis resistance in diffuse glioma: The potential therapeutic targets in the future.Frontiers in oncology · 2022Review
- Integrated lipidomics and proteomics reveal cardiolipin alterations, upregulation of HADHA and long chain fatty acids in pancreatic cancer stem cells.Scientific reports · 2021Article
- Capillary Zone Electrophoresis-Electron-Capture Collision-Induced Dissociation on a Quadrupole Time-of-Flight Mass Spectrometer for Top-Down Characterization of Intact Proteins.Journal of the American Society for Mass Spectrometry · 2021Article
- Mutational drivers of cancer cell migration and invasion.British journal of cancer · 2021Review
- Genetic Mutations and Variants in the Susceptibility of Familial Non-Medullary Thyroid Cancer.Genes · 2020Review
- Article
- MicroRNA‑200a promotes esophageal squamous cell carcinoma cell proliferation, migration and invasion through extensive target genes.Molecular medicine reports · 2020Article
- Multi-model functionalization of disease-associated PTEN missense mutations identifies multiple molecular mechanisms underlying protein dysfunction.Nature communications · 2020Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
Although a variety of genetic alterations have been found across cancer types, the identification and functional characterization of candidate driver genetic lesions in an individual patient and their translation into clinically actionable strategies remain major hurdles. Here, we use whole genome sequencing of a prostate cancer tumor, computational analyses, and experimental validation to identify and predict novel oncogenic activity arising from a point mutation in the phosphatase and tensin homolog (PTEN) tumor suppressor protein. We demonstrate that this mutation (p.A126G) produces an enzymatic gain-of-function in PTEN, shifting its function from a phosphoinositide (PI) 3-phosphatase to a phosphoinositide (PI) 5-phosphatase. Using cellular assays, we demonstrate that this gain-of-function activity shifts cellular phosphoinositide levels, hyperactivates the PI3K/Akt cell proliferation pathway, and exhibits increased cell migration beyond canonical PTEN loss-of-function mutants. These findings suggest that mutationally modified PTEN can actively contribute to well-defined hallmarks of cancer. Lastly, we demonstrate that these effects can be substantially mitigated through chemical PI3K inhibitors. These results demonstrate a new dysfunction paradigm for PTEN cancer biology and suggest a potential framework for the translation of genomic data into actionable clinical strategies for targeted patient therapy.
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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.