ArticleProceedings of the National Academy of Sciences of the United States of America2010
Activity of any class IA PI3K isoform can sustain cell proliferation and survival.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
82 citing papers in PubMed, 1 synthesis or guideline pooled it, 165 citations in OpenAlex.
- Knockdown of Tousled‑like kinase 1 inhibits survival of glioblastoma multiforme cells.International journal of molecular medicine · 2020Pooled it
- Pan-phosphatidylinositol 3-kinase inhibition with buparlisib in patients with relapsed or refractory non-Hodgkin lymphoma.Haematologica · 2017Trial
- A renaissance in targeting the PI3K/AKT/mTOR pathway.Nature reviews. Drug discovery · 2026Review
- Cooperative Roles of Class IA PI3K Isoforms in Translocation-Related Sarcoma Cell Survival and Proliferation.Cancer research communications · 2026Article
- Novel role for PI3Kβ in placental function through regulation of system A amino acid transporter expression, associated with embryonic lethality.Cellular and molecular life sciences : CMLS · 2025Article
- The role of the striatin family proteins in hippo signaling and cellular regulation.Cell & bioscience · 2025Article
- Review
- Article
- Red and blue LED light increases the survival rate of random skin flaps in rats after MRSA infection.Lasers in medical science · 2025Article
- Molecular Basis of Oncogenic PI3K Proteins.Cancers · 2024Review
- Unveiling the Therapeutic Potential of Folate-Dependent One-Carbon Metabolism in Cancer and Neurodegeneration.International journal of molecular sciences · 2024Review
- A class I PI3K signalling network regulates primary cilia disassembly in normal physiology and disease.Nature communications · 2024Article
- USP14 Regulates ATF2/PIK3CD Axis to Promote Microvascular Endothelial Cell Proliferation, Migration, and Angiogenesis in Diabetic Retinopathy.Biochemical genetics · 2023Article
- MicroRNA based combinatorial therapy against TKIs resistant CML by inactivating the PI3K/Akt/mTOR pathway: a review.Medical oncology (Northwood, London, England) · 2023Review
- Nuclear Phosphoinositides as Key Determinants of Nuclear Functions.Biomolecules · 2023Review
- Article
- Targeting Class I-II-III PI3Ks in Cancer Therapy: Recent Advances in Tumor Biology and Preclinical Research.Cancers · 2023Review
- Review
- BCL-2 inhibitor synergizes with PI3Kδ inhibitor and overcomes FLT3 inhibitor resistance in acute myeloid leukaemia.American journal of cancer research · 2022Article
- PI3K inhibitors are finally coming of age.Nature reviews. Drug discovery · 2021Review
22 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
5 authors at 3 institutions in 1 country.
Funding
Abstract
Small molecule inhibitors of PI3K for oncology mainly target the class I PI3Ks, comprising the p110alpha, beta, gamma, and delta isoforms, of which only p110alpha is mutated in cancer. To assess the roles of class I PI3K isoforms in cell proliferation and survival, we generated immortalized mouse leukocyte and fibroblast models in which class I PI3Ks were inactivated by genetic and pharmacological approaches. In IL3-dependent hemopoietic progenitor cells (which express all four class I PI3K isoforms), genetic inactivation of either p110alpha or p110delta did not affect cell proliferation or survival or sensitize to p110beta or p110gamma inactivation. Upon compound inactivation of p110alpha and p110delta, which removed >90% of p85-associated PI3K activity, remarkably, cells continued to proliferate effectively, with p110beta assuming an essential role in signaling and cell survival. Furthermore, under these conditions of diminished class I PI3K activity, input from the ERK pathway became important for cell survival. Similar observations were made in mouse embryonic fibroblasts (which mainly express p110alpha and p110beta) in which p110alpha or p110beta could sustain cell proliferation as a single isoform. Taken together, these data demonstrate that a small fraction of total class I PI3K activity is sufficient to sustain cell survival and proliferation. Persistent inhibition of selected PI3K isoforms can allow the remaining isoform(s) to couple to upstream signaling pathways in which they are not normally engaged. Such functional redundancy of class IA PI3K isoforms upon sustained PI3K inhibition has implications for the development and use of PI3K inhibitors in cancer.
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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.