ArticleCell death and differentiation2015
PTEN induces apoptosis and cavitation via HIF-2-dependent Bnip3 upregulation during epithelial lumen formation.
Article in Cell death and differentiation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 29 citations in OpenAlex.
- Drospirenone promotes apoptosis in ectopic but inhibits proliferation in eutopic human endometrial stromal cells.PloS one · 2026Article
- The Analysis of Embryoid Body Formation and Its Role in Retinal Organoid Development.International journal of molecular sciences · 2024Article
- Advanced glycation end products (AGEs) downregulate the miR-4429/PTEN axis to promote apoptosis of fibroblasts in pelvic organ prolapse.Annals of translational medicine · 2022Article
- The crosstalk between HIFs and mitochondrial dysfunctions in cancer development.Cell death & disease · 2021Review
- Cell Mechanics in Embryoid Bodies.Cells · 2020Review
- PTEN dephosphorylates Abi1 to promote epithelial morphogenesis.The Journal of cell biology · 2020Article
- PTEN suppresses epithelial-mesenchymal transition and cancer stem cell activity by downregulating Abi1.Scientific reports · 2020Article
- Target prediction and validation of microRNAs expressed from FSHR and aromatase genes in human ovarian granulosa cells.Scientific reports · 2020Article
- MicroRNAomic Transcriptomic Analysis Reveal Deregulation of Clustered Cellular Functions in Human Mesenchymal Stem Cells During in Vitro Passaging.Stem cell reviews and reports · 2020Article
- Differentiation of Induced Pluripotent Stem Cells towards Mesenchymal Stromal Cells is Hampered by Culture in 3D Hydrogels.Scientific reports · 2019Article
- Comparative Transcriptomic Analysis Reveals Molecular Profiles of Central Nervous System in Maternal Diapause Induction ofG3 (Bethesda, Md.) · 2019Article
- A clinical study on the expression of PTEN in renal cell carcinoma in children.Oncology letters · 2019Article
- The hypoxic tumour microenvironment.Oncogenesis · 2018Review
- Efficacy, long-term toxicity, and mechanistic studies of gold nanorods photothermal therapy of cancer in xenograft mice.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Autophagy Induction Results in Enhanced Anoikis Resistance in Models of Peritoneal Disease.Molecular cancer research : MCR · 2017Article
- Prognostic tissue biomarker exploration for patients with metastatic renal cell carcinoma receiving vascular endothelial growth factor receptor tyrosine kinase inhibitors.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Role of Intestinal HIF-2α in Health and Disease.Annual review of physiology · 2016Review
- TAp73 transcriptionally represses BNIP3 expression.Cell cycle (Georgetown, Tex.) · 2015Article
- Gene Perturbation Atlas (GPA): a single-gene perturbation repository for characterizing functional mechanisms of coding and non-coding genes.Scientific reports · 2015Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
The tumor suppressor phosphatase and tensin homolog (PTEN) dephosphorylates PIP3 and antagonizes the prosurvival PI3K-Akt pathway. Targeted deletion of PTEN in mice led to early embryonic lethality. To elucidate its role in embryonic epithelial morphogenesis and the underlying mechanisms, we used embryonic stem cell-derived embryoid body (EB), an epithelial cyst structurally similar to the periimplantation embryo. PTEN is upregulated during EB morphogenesis in parallel with apoptosis of core cells, which mediates EB cavitation. Genetic ablation of PTEN causes Akt overactivation, apoptosis resistance and cavitation blockade. However, rescue experiments using mutant PTEN and pharmacological inhibition of Akt suggest that the phosphatase activity of PTEN and Akt are not involved in apoptosis-mediated cavitation. Instead, hypoxia-induced upregulation of Bnip3, a proapoptotic BH3-only protein, mediates PTEN-dependent apoptosis and cavitation. PTEN inactivation inhibits hypoxia- and reactive oxygen species-induced Bnip3 elevation. Overexpression of Bnip3 in PTEN-null EBs rescues apoptosis of the core cells. Mechanistically, suppression of Bnip3 following PTEN loss is likely due to reduction of hypoxia-inducible factor-2α (HIF-2α) because forced expression of an oxygen-stable HIF-2α mutant rescues Bnip3 expression and apoptosis. Lastly, we show that HIF-2α is upregulated by PTEN at both transcriptional and posttranscriptional levels. Ablation of prolyl hydroxylase domain-containing protein 2 (PHD2) in normal EBs or inhibition of PHD activities in PTEN-null EBs stabilizes HIF-2α and induces Bnip3 and caspase-3 activation. Altogether, these results suggest that PTEN is required for apoptosis-mediated cavitation during epithelial morphogenesis by regulating the expression of HIF-2α and Bnip3.
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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.