ArticlePLoS genetics2021
Positive correlation between transcriptomic stemness and PI3K/AKT/mTOR signaling scores in breast cancer, and a counterintuitive relationship with PIK3CA genotype.
Article in PLoS genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- Three-dimensional spheroid models in breast cancer: tumor microenvironment complexity, cancer stem cell-driven resistance, and translational model integration.Journal of translational medicine · 2026Review
- HOXD10 promotes hepatocellular carcinoma progression by enhancing m6A methylation and activating the PI3K/AKT/mTOR pathway.Journal of translational medicine · 2026Article
- Computational decoding of cell-cycle phase effects on cancer hallmarks across breast cancer subtypes.Breast cancer research : BCR · 2025Article
- PI3 K/AKT/mTOR pathway and its role in breast cancer stem cells.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Article
- Emerging Mechanisms of Therapy Resistance in Metastatic ER+ Breast Cancer.Endocrinology · 2025Review
- The role of the mTOR pathway in breast cancer stem cells (BCSCs): mechanisms and therapeutic potentials.Stem cell research & therapy · 2025Review
- DNA methylation memory of pancreatic acinar-ductal metaplasia transition state altering Kras-downstream PI3K and Rho GTPase signaling in the absence of Kras mutation.Genome medicine · 2025Article
- Glycolysis-mTORC1 crosstalk drives proliferation of patient-derived endometrial cancer spheroid cells with ALDH activity.Cell death discovery · 2024Article
- Cancer stem cells: advances in knowledge and implications for cancer therapy.Signal transduction and targeted therapy · 2024Review
- Pathway Activation Analysis for Pan-Cancer Personalized Characterization Based on Riemannian Manifold.International journal of molecular sciences · 2024Article
- The mechanisms of class 1A PI3K and Wnt/β-catenin coupled signaling in breast cancer.Biochemical Society transactions · 2023Review
- Propofol inhibits colon cancer cell stemness and epithelial-mesenchymal transition by regulating SIRT1, Wnt/β-catenin and PI3K/AKT/mTOR signaling pathways.Discover oncology · 2023Article
- Genome-wide CRISPR knockout screening identified G protein pathway suppressor 2 as a novel tumor suppressor for uveal melanoma metastasis.Journal of cancer research and clinical oncology · 2023Article
- Deciphering Common Traits of Breast and Ovarian Cancer Stem Cells and Possible Therapeutic Approaches.International journal of molecular sciences · 2023Review
- Genomic characterisation of hormone receptor-positive breast cancer arising in very young women.Annals of oncology : official journal of the European Society for Medical Oncology · 2023Article
- Development and safety of PI3K inhibitors in cancer.Archives of toxicology · 2023Review
- Exosome-transmitted circCABIN1 promotes temozolomide resistance in glioblastoma via sustaining ErbB downstream signaling.Journal of nanobiotechnology · 2023Article
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Corrections and comments
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Authors and funding
8 authors at 5 institutions in 3 countries.
Funding
Abstract
A PI3Kα-selective inhibitor has recently been approved for use in breast tumors harboring mutations in PIK3CA, the gene encoding p110α. Preclinical studies have suggested that the PI3K/AKT/mTOR signaling pathway influences stemness, a dedifferentiation-related cellular phenotype associated with aggressive cancer. However, to date, no direct evidence for such a correlation has been demonstrated in human tumors. In two independent human breast cancer cohorts, encompassing nearly 3,000 tumor samples, transcriptional footprint-based analysis uncovered a positive linear association between transcriptionally-inferred PI3K/AKT/mTOR signaling scores and stemness scores. Unexpectedly, stratification of tumors according to PIK3CA genotype revealed a "biphasic" relationship of mutant PIK3CA allele dosage with these scores. Relative to tumor samples without PIK3CA mutations, the presence of a single copy of a hotspot PIK3CA variant was associated with lower PI3K/AKT/mTOR signaling and stemness scores, whereas the presence of multiple copies of PIK3CA hotspot mutations correlated with higher PI3K/AKT/mTOR signaling and stemness scores. This observation was recapitulated in a human cell model of heterozygous and homozygous PIK3CAH1047R expression. Collectively, our analysis (1) provides evidence for a signaling strength-dependent PI3K-stemness relationship in human breast cancer; (2) supports evaluation of the potential benefit of patient stratification based on a combination of conventional PI3K pathway genetic information with transcriptomic indices of PI3K signaling activation.
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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 Socratic graph.