ArticleNature communications2020
p85β regulates autophagic degradation of AXL to activate oncogenic signaling.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 46 citations in OpenAlex.
- Phase separation of p85β modulates hepatocellular carcinoma progression through POLR1A.International journal of biological sciences · 2026Article
- TRIM2 exacerbates the advancement of idiopathic pulmonary fibrosis by modulating β-catenin and endoplasmic reticulum stress.European journal of medical research · 2025Article
- p85β acts as a transcription cofactor and cooperates with BCLAF1 in the nucleus.Nature communications · 2025Article
- STAMBPL1/TRIM21 Balances AXL Stability Impacting Mesenchymal Phenotype and Immune Response in KIRC.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Thiophene-Linked 1,2,4-Triazoles: Synthesis, Structural Insights and Antimicrobial and Chemotherapeutic Profiles.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Genomic analyses of germline and somatic variation in high-grade serous ovarian cancer.Journal of ovarian research · 2023Article
- YWHAB knockdown inhibits cell proliferation whilst promoting cell cycle arrest and apoptosis in colon cancer cells through PIK3R2.Experimental and therapeutic medicine · 2023Article
- Genomic Analyses of Germline and Somatic Variation in High-Grade Serous Ovarian Cancer.Research square · 2023Article
- Epigenetic and post-translational modifications in autophagy: biological functions and therapeutic targets.Signal transduction and targeted therapy · 2023Review
- Divergent roles of the regulatory subunits of class IA PI3K.Frontiers in endocrinology · 2023Review
- The Promising Therapeutic Approaches for Radiation-Induced Pulmonary Fibrosis: Targeting Radiation-Induced Mesenchymal Transition of Alveolar Type II Epithelial Cells.International journal of molecular sciences · 2022Review
- Article
- lncRNA XLOC013218 promotes cell proliferation and TMZ resistance by targeting the PIK3R2-mediated PI3K/AKT pathway in glioma.Cancer science · 2022Article
- Endosomal LC3C-pathway selectively targets plasma membrane cargo for autophagic degradation.Nature communications · 2022Article
- Interfering with the expression of EEF1D gene enhances the sensitivity of ovarian cancer cells to cisplatin.BMC cancer · 2022Article
- MicroRNA-135b-5p regulates trophoblast cell function by targeting phosphoinositide-3-kinase regulatory subunit 2 in preeclampsia.Bioengineered · 2022Article
- Expression and Role of TRIM2 in Human Diseases.BioMed research international · 2022Review
- p85β alters response to EGFR inhibitor in ovarian cancer through p38 MAPK-mediated regulation of DNA repair.Neoplasia (New York, N.Y.) · 2021Article
- Megalencephalic leukoencephalopathy with subcortical cysts 1 (MLC1) promotes glioblastoma cell invasion in the brain microenvironment.Oncogene · 2020Article
- Oncogenic pathway driven by p85β: upstream signals to activate p110.Molecular & cellular oncology · 2020Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 3 countries.
Funding
Abstract
PIK3R2 encodes the p85β regulatory subunit of phosphatidylinositol 3-kinase and is frequently amplified in cancers. The signaling mechanism and therapeutic implication of p85β are poorly understood. Here we report that p85β upregulates the protein level of the receptor tyrosine kinase AXL to induce oncogenic signaling in ovarian cancer. p85β activates p110 activity and AKT-independent PDK1/SGK3 signaling to promote tumorigenic phenotypes, which are all abolished upon inhibition of AXL. At the molecular level, p85β alters the phosphorylation of TRIM2 (an E3 ligase) and optineurin (an autophagy receptor), which mediate the selective regulation of AXL by p85β, thereby disrupting the autophagic degradation of the AXL protein. Therapeutically, p85β expression renders ovarian cancer cells vulnerable to inhibitors of AXL, p110, or PDK1. Conversely, p85β-depleted cells are less sensitive to these inhibitors. Together, our findings provide a rationale for pharmacological blockade of the AXL signaling axis in PIK3R2-amplified ovarian 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.