ArticleNature communications2019
Deregulated Gab2 phosphorylation mediates aberrant AKT and STAT3 signaling upon PIK3R1 loss in ovarian cancer.
Article in Nature communications, 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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Who cites it
32 citing papers in PubMed, 49 citations in OpenAlex.
- LncRNA TRHDE-AS1 functions as a tumor suppressor in ovarian cancer via the miR-17-5p/PIK3R1 ceRNA regulatory axis.Journal of molecular histology · 2026Article
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- Network pharmacological analysis and experimental study of cucurbitacin B in oral squamous cell carcinoma.Molecular diversity · 2024Article
- Herb pair of Huangqi-Danggui exerts anti-tumor immunity to breast cancer by upregulating PIK3R1.Animal models and experimental medicine · 2024Article
- Network Pharmacology and Molecular Docking Identify the Potential Mechanism and Therapeutic Role ofDrug design, development and therapy · 2024Article
- Long non-coding RNA JPX promotes endometrial carcinoma progression via janus kinase 2/signal transducer and activator of transcription 3.Frontiers in oncology · 2024Article
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- FBXO21 mediated degradation of p85α regulates proliferation and survival of acute myeloid leukemia.Leukemia · 2023Article
- Resistance mechanism to Notch inhibition and combination therapy in human T-cell acute lymphoblastic leukemia.Blood advances · 2023Article
- Characteristics of circulating small noncoding RNAs in plasma and serum during human aging.Aging medicine (Milton (N.S.W)) · 2023Article
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- Low expression of m6A reader YTHDC1 promotes progression of ovarian cancer via PIK3R1/STAT3/GANAB axis.International journal of biological sciences · 2023Article
- State of the Biomarker Science in Ovarian Cancer: A National Cancer Institute Clinical Trials Planning Meeting Report.JCO precision oncology · 2022Article
- Skeletal muscle-specific overexpression of miR-486 limits mammary tumor-induced skeletal muscle functional limitations.Molecular therapy. Nucleic acids · 2022Article
- Classical Signaling and Trans-Signaling Pathways Stimulated byInternational journal of molecular sciences · 2022Article
- STAT3 exerts pro-tumor and anti-autophagy roles in cervical cancer.Diagnostic pathology · 2022Article
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
Copy number loss of PIK3R1 (p85α) most commonly occurs in ovarian cancer among all cancer types. Here we report that ovarian cancer cells manifest a spectrum of tumorigenic phenotypes upon knockdown of PIK3R1. PIK3R1 loss activates AKT and p110-independent JAK2/STAT3 signaling through inducing changes in the phosphorylation of the docking protein Gab2, thereby relieving the negative inhibition on AKT and promoting the assembly of JAK2/STAT3 signalosome, respectively. Additional mechanisms leading to AKT activation include enhanced p110α kinase activity and a decrease in PTEN level. PIK3R1 loss renders ovarian cancer cells vulnerable to inhibition of AKT or JAK2/STAT3. The combination of AKT and STAT3 inhibitors significantly increases the anti-tumor effect compared to single-agent treatments. Together, our findings provide a rationale for mechanism-based therapeutic approach that targets tumors with loss of PIK3R1.
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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.