ArticleProceedings of the National Academy of Sciences of the United States of America2014
PI3K isoform dependence of PTEN-deficient tumors can be altered by the genetic context.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 70 citations in OpenAlex.
- Loss of the tumor suppressor PTEN activates cell-intrinsic interferon signaling to drive immune resistance.Genes & development · 2026Article
- Loss of the tumor suppressor PTEN activates cell-intrinsic interferon signaling to drive immune resistance.bioRxiv : the preprint server for biology · 2025Article
- NOS inhibition sensitizes metaplastic breast cancer to PI3K inhibition and taxane therapy via c-JUN repression.Nature communications · 2024Article
- SP1 Mediated PIK3CB Upregulation Promotes Gastric Carcinogenesis.Journal of Cancer · 2024Article
- Review
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- Breast cancer brain metastasis: Current evidence and future directions.Cancer medicine · 2023Review
- An Insight into Molecular Targets of Breast Cancer Brain Metastasis.International journal of molecular sciences · 2022Review
- Targeting Cell Cycle Progression in HER2+ Breast Cancer: An Emerging Treatment Opportunity.International journal of molecular sciences · 2022Review
- PIPFEBS letters · 2022Article
- The role of PI3'-lipid signalling in melanoma initiation, progression and maintenance.Experimental dermatology · 2022Review
- Class I PI3K Biology.Current topics in microbiology and immunology · 2022Article
- AKT Degradation Selectively Inhibits the Growth of PI3K/PTEN Pathway-Mutant Cancers with Wild-Type KRAS and BRAF by Destabilizing Aurora Kinase B.Cancer discovery · 2021Article
- PI3K inhibitors are finally coming of age.Nature reviews. Drug discovery · 2021Review
- Defining the therapeutic selective dependencies for distinct subtypes of PI3K pathway-altered prostate cancers.Nature communications · 2021Article
- Plasma Cell-Free DNA Profiling of PTEN-PI3K-AKT Pathway Aberrations in Metastatic Castration-Resistant Prostate Cancer.JCO precision oncology · 2021Article
- A tipping-point for apoptosis following dual inhibition of HER2 signaling network by T-DM1 plus GDC-0980 maximizes anti-tumor efficacy.American journal of cancer research · 2021Article
- Divergent Roles of PI3K Isoforms in PTEN-Deficient Glioblastomas.Cell reports · 2020Article
- Molecular and cellular mechanisms underlying brain metastasis of breast cancer.Cancer metastasis reviews · 2020Review
- Combined targeting of G protein-coupled receptor and EGF receptor signaling overcomes resistance to PI3K pathway inhibitors in PTEN-null triple negative breast cancer.EMBO molecular medicine · 2020Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
There has been increasing interest in the use of isoform-selective inhibitors of phosphatidylinositide-3-kinase (PI3K) in cancer therapy. Using conditional deletion of the p110 catalytic isoforms of PI3K to predict sensitivity of cancer types to such inhibitors, we and others have demonstrated that tumors deficient of the phosphatase and tensin homolog (PTEN) are often dependent on the p110β isoform of PI3K. Because human cancers usually arise due to multiple genetic events, determining whether other genetic alterations might alter the p110 isoform requirements of PTEN-null tumors becomes a critical question. To investigate further the roles of p110 isoforms in PTEN-deficient tumors, we used a mouse model of ovarian endometrioid adenocarcinoma driven by concomitant activation of the rat sarcoma protein Kras, which is known to activate p110α, and loss of PTEN. In this model, ablation of p110β had no effect on tumor growth, whereas p110α ablation blocked tumor formation. Because ablation of PTEN alone is often p110β dependent, we wondered if the same held true in the ovary. Because PTEN loss alone in the ovary did not result in tumor formation, we tested PI3K isoform dependence in ovarian surface epithelium (OSE) cells deficient in both PTEN and p53. These cells were indeed p110β dependent, whereas OSEs expressing activated Kras with or without PTEN loss were p110α dependent. Furthermore, isoform-selective inhibitors showed a similar pattern of the isoform dependence in established Kras(G12D)/PTEN-deficient tumors. Taken together, our data suggest that, whereas in some tissues PTEN-null tumors appear to inherently depend on p110β, the p110 isoform reliance of PTEN-deficient tumors may be altered by concurrent mutations that activate p110α.
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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.