The DOI matches its Crossref record; 67 of the 67 references it cites were found in a registry or an index.
Senescent cells develop a parp-1 and nuclear factor-κB-associated secretome (PNAS).
Open accessAbstract
Melanoma cells can enter the process of senescence, but whether they express a secretory phenotype, as reported for other cells, is undetermined. This is of paramount importance, because this secretome can alter the tumor microenvironment and the response to chemotherapeutic drugs. More generally, the molecular events involved in formation of the senescent-associated secretome have yet to be determined. We reveal here that melanoma cells experiencing senescence in response to diverse stimuli, including anti-melanoma drugs, produce an inflammatory secretory profile, where the chemokine ligand-2 (CCL2) acts as a critical effector. Thus, we reveal how senescence induction might be involved in therapeutic failure in melanoma. We further provide a molecular relationship between senescence induction and secretome formation by revealing that the poly(ADP-ribose) polymerase-1 (PARP-1)/nuclear factor-κB (NF-κB) signaling cascade, activated during senescence, drives the formation of a secretome endowed with protumoral and prometastatic properties. Our findings also point to the existence of the PARP-1 and NF-κB-associated secretome, termed the PNAS, in nonmelanoma cells. Most importantly, inhibition of PARP-1 or NF-κB prevents the proinvasive properties of the secretome. Collectively, identification of the PARP-1/NF-κB axis in secretome formation opens new avenues for therapeutic intervention against cancers.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Chemotherapeutic drugs or oxidative stress induced DNA damage engage PARP-1/ATM/NF-κB signaling cascade to induce senescence in melanoma and non-melanoma cells (Ohanna et al., 2011).”
From Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype (2021) · cites this paper as Ohanna et al., 2011
Experimental — accuracy not yet measuredIn the citing paper
“Blocking PARP-1, ATM, or NF-κB in melanoma cells prevents the secretion of chemokine CCL2 thereby restricting the deleterious pro-invasive properties of the inflammatory SASP mediated by PNAS (Ohanna et al., 2011).”
From Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype (2021) · cites this paper as Ohanna et al., 2011
In the citing paper
“These senescent cells develop a PARP-1 and NF-κB associated secretome (PNAS) containing chemokine CCL2 along with other SASP factors thereby augmenting the invasiveness of melanoma cells which might have escaped senescence.”
From Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype (2021) · cites this paper as Ohanna et al., 2011
In the citing paper
“some tumor cells can enter senescence in response to DNA damaging therapies [363,364].”
From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [364]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
1 retracted
Ionizing radiation-induced NF-κB activation requires PARP-1 function to confer radioresistance
Veuger, S. J., Hunter, J. E., & Durkacz, B. W. (2008) · Oncogene · doi:10.1038/onc.2008.439 · Cited by 134
RetractedOncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a
Serrano, M., Lin, A. W., McCurrach, M. E., Beach, D., & Lowe, S. W. (1997) · Cell · doi:10.1016/s0092-8674(00)81902-9 · Cited by 5,218 · cited 1×
“Ordinarily, senescence is a process arising in normal cells in response to telomere erosion or oncogenic stress, acting through checkpoint activation and cell cycle arrest as a barrier to tumorigenesis (Serrano et al. 1997; Steinert et al. 2000).”
BackgroundThe senescence-associated secretory phenotype: the dark side of tumor suppression
Coppé, J.-P., Desprez, P.-Y., Krtolica, A., & Campisi, J. (2010) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-121808-102144 · Cited by 5,206
The Nuclear Factor NF- B Pathway in InflammationPreprint
Lawrence, T. (2009) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a001651 · Cited by 5,126
Hartwell, L. H., & Kastan, M. B. (1994) · Science · doi:10.1126/science.7997877 · Cited by 2,539
Oncogene-Induced Senescence Relayed by an Interleukin-Dependent Inflammatory Network
Kuilman, T., Michaloglou, C., Vredeveld, L. C. W., Douma, S., van Doorn, R., Desmet, C. J., Aarden, L. A., Mooi, W. J., & Peeper, D. S. (2008) · Cell · doi:10.1016/j.cell.2008.03.039 · Cited by 2,086
Cell Cycle Checkpoints: Preventing an Identity Crisis
Elledge, S. J. (1996) · Science · doi:10.1126/science.274.5293.1664 · Cited by 2,050
Chemokine signaling via the CXCR2 receptor reinforces senescence
Acosta, J. C., O'Loghlen, A., Banito, A., Guijarro, M. V., Augert, A., Raguz, S., Fumagalli, M., Da Costa, M., Brown, C., Popov, N., et al. (2008) · Cell · doi:10.1016/j.cell.2008.03.038 · Cited by 1,801 · cited 1×
“Some of these factors display cell-autonomous activity and work to reinforce the senescence program (Acosta et al. 2008; Kuilman et al. 2008).”
BackgroundKrtolica, A., Parrinello, S., Lockett, S., Desprez, P.-Y., & Campisi, J. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.211053698 · Cited by 1,730
DNA repair pathways as targets for cancer therapy
Helleday, T., Petermann, E., Lundin, C., Hodgson, B., & Sharma, R. A. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2342 · Cited by 1,666
Cited by
Sorted by citations
Hallmarks of Cellular Senescence
Hernandez-Segura, A., Nehme, J., & Demaria, M. (2018) · Trends in Cell Biology · doi:10.1016/j.tcb.2018.02.001 · Cited by 2,605
Cellular senescence in aging and age-related disease: from mechanisms to therapy
Childs, B. G., Durik, M., Baker, D. J., & van Deursen, J. M. (2015) · Nature Medicine · doi:10.1038/nm.4000 · Cited by 2,363
Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype
Kumari, R., & Jat, P. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.645593 · Cited by 1,622
The senescence-associated secretory phenotype and its physiological and pathological implications
Wang, B., Han, J., Elisseeff, J. H., & Demaria, M. (2024) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-024-00727-x · Cited by 948
Senescence and cancer — role and therapeutic opportunities
Schmitt, C. A., Wang, B., & Demaria, M. (2022) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-022-00668-4 · Cited by 794
Metadata
- Authors
- Ohanna, M., Giuliano, S., Bonet, C., Imbert, V., Hofman, V., Zangari, J., Bille, K., Robert, C., Bressac-de Paillerets, B., Hofman, P., Rocchi, S., Peyron, J.-F., Lacour, J.-P., Ballotti, R., & Bertolotto, C.
- Affiliations
- Inserm (FR)
- Institut Gustave Roussy (FR)
- Centre Hospitalier Universitaire de Nice (FR)
- ORCID
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2011-06-06
- Volume
- 25
- Issue
- 12
- Pages
- 1245-1261
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC3127427
- OpenAlex
- W2162942873
- Cited by
- 267
- References
- 67
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 17 · 2023: 24 · 2022: 20 · 2021: 33 · 2020: 25 · 2019: 15 · 2018: 16 · 2017: 13 · 2016: 16 · 2015: 17 · 2014: 13 · 2013: 21 · 2012: 15
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Association pour la Recherche sur le Cancer
- Institut National de la Santé et de la Recherche Médicale
- Fondation de France
- Institut National Du Cancer
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- cellular senescence, senescence-associated secretome, melanoma, PARP1, NF-κB signaling, MCP-1, chemokines, tumor microenvironment, chemoresistance, metastasis, tumor invasion
- MeSH terms
- Poly (ADP-Ribose) Polymerase-1, DNA Damage, Humans, Melanoma, Neoplasm Invasiveness, Poly(ADP-ribose) Polymerases, Signal Transduction, Gene Expression Regulation, Neoplastic, NF-kappa B, Cellular Senescence, Chemokine CCL2, Gene Expression Profiling, Cell Line, Tumor
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
