ArticleClinical cancer research : an official journal of the American Association for Cancer Research2013
PI3K pathway dependencies in endometrioid endometrial cancer cell lines.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers, 1 of them a synthesis that pooled it.
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Who cites it
79 citing papers in PubMed, 1 synthesis or guideline pooled it, 137 citations in OpenAlex.
- Identifying molecular mediators of the relationship between body mass index and endometrial cancer risk: a Mendelian randomization analysis.BMC medicine · 2022Pooled it
- Dual PI3K/AKT/mTOR and CDK4/6 inhibition suppresses survivin to overcome uterine dedifferentiated endometrial carcinoma.Cancer gene therapy · 2026Article
- PTEN Loss Promotes PI3Kβ Phosphorylation and EPHA2/SRC/p-PI3KβY962 Complex Assembly to Drive Tumorigenesis.Cancer discovery · 2026Article
- Evolutionary perspectives on endometrial cancer: antagonistic pleiotropy.Molecular & cellular oncology · 2026Review
- Evolution and Co-occurrence of PI3K Pathway Gene Mutations in Endometrial Carcinoma Molecular Subtypes at the Single-Cell Level.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Review
- Article
- PELP1 inhibition by SMIP34 reduces endometrial cancer progression via attenuation of ribosomal biogenesis.Molecular oncology · 2024Article
- Advances in research on autophagy mechanisms in resistance to endometrial cancer treatment.Frontiers in oncology · 2024Review
- Exposure to select PFAS and PFAS mixtures alters response to platinum-based chemotherapy in endometrial cancer cell lines.Environmental health : a global access science source · 2023Article
- Article
- PTEN-negative endometrial cancer cells protect their genome through enhanced DDB2 expression associated with augmented nucleotide excision repair.BMC cancer · 2023Article
- Mitochondrial Dysfunction Involved in the Cytotoxicity of Tramadol in Human Endometrial Carcinoma Cells.International journal of molecular sciences · 2022Article
- Proteomic and functional characterization of intra-tumor heterogeneity in human endometrial cancer.Cell reports. Medicine · 2022Article
- PTP1B inhibitors protect against acute lung injury and regulate CXCR4 signaling in neutrophils.JCI insight · 2022Article
- KDM1A inhibition augments the efficacy of rapamycin for the treatment of endometrial cancer.Cancer letters · 2022Article
- Article
- Antitumor activity of everolimus in recurrent metastatic endometrial cancer withGland surgery · 2021Article
- ENDOG Impacts on Tumor Cell Proliferation and Tumor Prognosis in the Context of PI3K/PTEN Pathway Status.Cancers · 2021Article
- Immune-related geneTranslational cancer research · 2021Article
19 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 4 institutions in 2 countries.
Funding
Abstract
purposeEndometrioid endometrial cancers (EEC) frequently harbor coexisting mutations in phosphoinositide 3-kinase (PI3K) pathway genes, including PTEN, PIK3CA, PIK3R1, and KRAS. We sought to define the genetic determinants of PI3K pathway inhibitor response in EEC cells, and whether PTEN-mutant EEC cell lines rely on p110β signaling for survival. EXPERIMENTAL
designTwenty-four human EEC cell lines were characterized for their mutation profile and activation state of PI3K and mitogen-activated protein kinase (MAPK) signaling pathway proteins. Cells were treated with pan-class I PI3K, p110α, and p110β isoform-specific, allosteric mTOR, mTOR kinase, dual PI3K/mTOR, mitogen-activated protein/extracellular signal-regulated kinase (MEK), and RAF inhibitors. RNA interference (RNAi) was used to assess effects of KRAS silencing in EEC cells.
resultsEEC cell lines harboring PIK3CA and PTEN mutations were selectively sensitive to the pan-class I PI3K inhibitor GDC-0941 and allosteric mTOR inhibitor temsirolimus, respectively. Subsets of EEC cells with concurrent PIK3CA and/or PTEN and KRAS mutations were sensitive to PI3K pathway inhibition, and only 2 of 6 KRAS-mutant cell lines showed response to MEK inhibition. KRAS RNAi silencing did not induce apoptosis in KRAS-mutant EEC cells. PTEN-mutant EEC cell lines were resistant to the p110β inhibitors GSK2636771 and AZD6482, and only in combination with the p110α selective inhibitor A66 was a decrease in cell viability observed.
conclusionsTargeted pan-PI3K and mTOR inhibition in EEC cells may be most effective in PIK3CA- and PTEN-mutant tumors, respectively, even in a subset of EECs concurrently harboring KRAS mutations. Inhibition of p110β alone may not be sufficient to sensitize PTEN-mutant EEC cells and combination with other targeted agents may be required.
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