ArticleCell death and differentiation2016
Heparan sulfation is essential for the prevention of cellular senescence.
Article in Cell death and differentiation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 43 citations in OpenAlex.
- An integrated multi-algorithm analysis to decipher senescence and metabolic characteristics in nucleus pulposus cells during disc degeneration.GeroScience · 2026Article
- Chemical Strategies for Controlling Sulfation in Biomacromolecules.ACS chemical biology · 2026Review
- FLRT2 prevents endothelial cell senescence and vascular aging by regulating the ITGB4/mTORC2/p53 signaling pathway.JCI insight · 2024Article
- Host-microbiome orchestration of the sulfated metabolome.Nature chemical biology · 2024Review
- Article
- Aging microenvironment and antitumor immunity for geriatric oncology: the landscape and future implications.Journal of hematology & oncology · 2023Review
- Heparan sulfate proteoglycans in cancer: Pathogenesis and therapeutic potential.Advances in cancer research · 2023Article
- New developments in the biology of fibroblast growth factors.WIREs mechanisms of disease · 2022Review
- Inhibition of p53 Sulfoconjugation Prevents Oxidative Hepatotoxicity and Acute Liver Failure.Gastroenterology · 2022Article
- An Integrated Proteomics and Bioinformatics Analysis of the Anticancer Properties of RT2 Antimicrobial Peptide on Human Colon Cancer (Caco-2) Cells.Molecules (Basel, Switzerland) · 2022Article
- A metabolism-related gene signature for predicting the prognosis in thyroid carcinoma.Frontiers in genetics · 2022Article
- Identification of senescence-associated long non-coding RNAs to predict prognosis and immune microenvironment in patients with hepatocellular carcinoma.Frontiers in genetics · 2022Article
- Review
- Heparanase and the hallmarks of cancer.Journal of translational medicine · 2020Review
- A novel long noncoding RNA Linc-ASEN represses cellular senescence through multileveled reduction of p21 expression.Cell death and differentiation · 2020Article
- Article
- Enhanced PAPSS2/VCAN sulfation axis is essential for Snail-mediated breast cancer cell migration and metastasis.Cell death and differentiation · 2019Article
- Integrin α6β4-Src-AKT signaling induces cellular senescence by counteracting apoptosis in irradiated tumor cells and tissues.Cell death and differentiation · 2019Article
- The Post-amyloid Era in Alzheimer's Disease: Trust Your Gut Feeling.Frontiers in aging neuroscience · 2019Review
- UDP-glucose Dehydrogenase: The First-step Oxidation Is an NADInternational journal of biological sciences · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cellular senescence is considered as an important tumor-suppressive mechanism. Here, we demonstrated that heparan sulfate (HS) prevents cellular senescence by fine-tuning of the fibroblast growth factor receptor (FGFR) signaling pathway. We found that depletion of 3'-phosphoadenosine 5'-phosphosulfate synthetase 2 (PAPSS2), a synthetic enzyme of the sulfur donor PAPS, led to premature cell senescence in various cancer cells and in a xenograft tumor mouse model. Sodium chlorate, a metabolic inhibitor of HS sulfation also induced a cellular senescence phenotype. p53 and p21 accumulation was essential for PAPSS2-mediated cellular senescence. Such senescence phenotypes were closely correlated with cell surface HS levels in both cancer cells and human diploid fibroblasts. The determination of the activation of receptors such as FGFR1, Met, and insulin growth factor 1 receptor β indicated that the augmented FGFR1/AKT signaling was specifically involved in premature senescence in a HS-dependent manner. Thus, blockade of either FGFR1 or AKT prohibited p53 and p21 accumulation and cell fate switched from cellular senescence to apoptosis. In particular, desulfation at the 2-O position in the HS chain contributed to the premature senescence via the augmented FGFR1 signaling. Taken together, we reveal, for the first time, that the proper status of HS is essential for the prevention of cellular senescence. These observations allowed us to hypothesize that the FGF/FGFR signaling system could initiate novel tumor defenses through regulating premature senescence.
Indexed as
Identifiers
What OpenQuestion holds
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.