ArticleNeoplasia (New York, N.Y.)2021
p85β alters response to EGFR inhibitor in ovarian cancer through p38 MAPK-mediated regulation of DNA repair.
Article in Neoplasia (New York, N.Y.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 18 citations in OpenAlex.
- From HPV infection to cervical precancer: Molecular mechanisms, immune microenvironment and emerging technologies.Cellular and molecular life sciences : CMLS · 2026Review
- PLSCR1 drives chemoresistance in TNBC via METTL3/IGF2BP3-mediated mRNA stabilization and EGFR-MAPK pathway activation.Cell death & disease · 2026Article
- Phase separation of p85β modulates hepatocellular carcinoma progression through POLR1A.International journal of biological sciences · 2026Article
- A multiscale model reveals how ERK/p38-regulated dormancy shapes tumor-immune dynamics and immunoediting outcomes.Frontiers in immunology · 2026Article
- Natural Metabolites as Modulators of Sensing and Signaling Mechanisms: Unlocking Anti-Ovarian Cancer Potential.Biomedicines · 2025Review
- SPTLC2 drives an EGFR-FAK-HBEGF signaling axis to promote ovarian cancer progression.Oncogene · 2025Article
- Mechanisms of the JNK/p38 MAPK signaling pathway in drug resistance in ovarian cancer.Frontiers in oncology · 2025Review
- Exploring glioma heterogeneity through omics networks: from gene network discovery to causal insights and patient stratification.BioData mining · 2024Article
- Tyrosine phosphatase SHP2 promoted the progression of CRC via modulating the PI3K/BRD4/TFEB signaling induced ferroptosis.Discover oncology · 2024Article
- Single cell lineage tracing reveals clonal dynamics of anti-EGFR therapy resistance in triple negative breast cancer.Genome medicine · 2024Article
- Identification of serum miR-1246 and miR-150-5p as novel diagnostic biomarkers for high-grade serous ovarian cancer.Scientific reports · 2023Article
- Adverse Toxic Effects of Tyrosine Kinase Inhibitors on Non-Target Zebrafish Liver (ZFL) Cells.International journal of molecular sciences · 2023Article
- Role of p38 MAP kinase in cancer stem cells and metastasis.Oncogene · 2022Review
- Review
- Expression and Role of TRIM2 in Human Diseases.BioMed research international · 2022Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
EGFR signaling promotes ovarian cancer tumorigenesis, and high EGFR expression correlates with poor prognosis. However, EGFR inhibitors alone have demonstrated limited clinical benefit for ovarian cancer patients, owing partly to tumor resistance and the lack of predictive biomarkers. Cotargeting EGFR and the PI3K pathway has been previously shown to yield synergistic antitumor effects in ovarian cancer. Therefore, we reasoned that PI3K may affect cellular response to EGFR inhibition. In this study, we revealed PI3K isoform-specific effects on the sensitivity of ovarian cancer cells to the EGFR inhibitor erlotinib. Gene silencing of PIK3CA (p110α) and PIK3CB (p110β) rendered cells more susceptible to erlotinib. In contrast, low expression of PIK3R2 (p85β) was associated with erlotinib resistance. Depletion of PIK3R2, but not PIK3CA or PIK3CB, led to increased DNA damage and reduced level of the nonhomologous end joining DNA repair protein BRD4. Intriguingly, these defects in DNA repair were reversed upon erlotinib treatment, which caused activation and nuclear import of p38 MAPK to promote DNA repair with increased protein levels of 53BP1 and BRD4 and foci formation of 53BP1. Remarkably, inhibition of p38 MAPK or BRD4 re-sensitized PIK3R2-depleted cells to erlotinib. Collectively, these data suggest that p38 MAPK activation and the subsequent DNA repair serve as a resistance mechanism to EGFR inhibitor. Combined inhibition of EGFR and p38 MAPK or DNA repair may maximize the therapeutic potential of EGFR inhibitor in ovarian cancer.
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