ArticleCell death and differentiation2020
A functional genetic screen defines the AKT-induced senescence signaling network.
Article in Cell death and differentiation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 68 citations in OpenAlex.
- SenFlag gene signature identifies senescent cells in mouse and human tissues through a conserved core transcriptional program.The EMBO journal · 2026Article
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- ERKed by too much signaling: from oncogenic driver to therapeutic vulnerability.Cellular and molecular life sciences : CMLS · 2026Review
- Decoding the tumor-aging axis: from bench to clinical.Frontiers in immunology · 2026Review
- Analysis of senescence in pituitary tumors from different lineages and the potential role of senolytic drugs as targeted therapies.Frontiers in endocrinology · 2026Article
- Glucosamine mitigates hyperglycemic-induced oxidative stress via the SIRT1 pathway in human corneal epithelial cells.Scientific reports · 2025Article
- Exploiting dysregulated iron homeostasis to eradicate persistent high-grade serous ovarian cancer.Cell death discovery · 2025Article
- Ap1s1 reduction in the aging brain heightens neuronal vulnerability to amyloid-β and oxidative stress in Alzheimer's pathogenesis.Alzheimer's research & therapy · 2025Article
- Mutations in tumor signaling, metastases, and synthetic lethality establish distinct patterns.PLoS computational biology · 2025Article
- The Inositol-5-Phosphatase SHIP1: Expression, Regulation and Role in Acute Lymphoblastic Leukemia.International journal of molecular sciences · 2025Review
- A transcriptome-based human universal senescence index (hUSI) robustly predicts cellular senescence under various conditions.Nature aging · 2025Article
- Integrated multi-omics analysis and experimental verification reveal the involvement of the PI3K/Akt signaling pathway in myometrial fibrosis of adenomyosis.Scientific reports · 2025Article
- PseudoCell: A Multivalued Logical Regulatory Network to Investigate Premature Senescence Dynamics and Heterogeneity.Aging medicine (Milton (N.S.W)) · 2025Article
- Fibroblasts in heterotopic ossification: mechanisms and therapeutic targets.International journal of biological sciences · 2025Review
- Review
- All-trans retinoic acid inhibits glioblastoma progression and attenuates radiation-induced brain injury.JCI insight · 2024Article
- Co-occurring Mutations in Different Genes Can Fuel Oncogenic Signaling and Serve as Metastatic Tumor Markers.bioRxiv : the preprint server for biology · 2024Article
- Senescent cells and macrophages cooperate through a multi-kinase signaling network to promote intestinal transformation in Drosophila.Developmental cell · 2024Article
- Lactic acid promotes nucleus pulposus cell senescence and corresponding intervertebral disc degeneration via interacting with Akt.Cellular and molecular life sciences : CMLS · 2024Article
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Exquisite regulation of PI3K/AKT/mTORC1 signaling is essential for homeostatic control of cell growth, proliferation, and survival. Aberrant activation of this signaling network is an early driver of many sporadic human cancers. Paradoxically, sustained hyperactivation of the PI3K/AKT/mTORC1 pathway in nontransformed cells results in cellular senescence, which is a tumor-suppressive mechanism that must be overcome to promote malignant transformation. While oncogene-induced senescence (OIS) driven by excessive RAS/ERK signaling has been well studied, little is known about the mechanisms underpinning the AKT-induced senescence (AIS) response. Here, we utilize a combination of transcriptome and metabolic profiling to identify key signatures required to maintain AIS. We also employ a whole protein-coding genome RNAi screen for AIS escape, validating a subset of novel mediators and demonstrating their preferential specificity for AIS as compared with OIS. As proof of concept of the potential to exploit the AIS network, we show that neurofibromin 1 (NF1) is upregulated during AIS and its ability to suppress RAS/ERK signaling facilitates AIS maintenance. Furthermore, depletion of NF1 enhances transformation of p53-mutant epithelial cells expressing activated AKT, while its overexpression blocks transformation by inducing a senescent-like phenotype. Together, our findings reveal novel mechanistic insights into the control of AIS and identify putative senescence regulators that can potentially be targeted, with implications for new therapeutic options to treat PI3K/AKT/mTORC1-driven cancers.
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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.