Cited by 267Telomeres, Telomerase, and SenescenceNF-κB Signaling PathwaysCell death mechanisms and regulation

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).

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Abstract

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.

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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)
Venue
Genes & Development
Published
2011-06-06
Volume
25
Issue
12
Pages
1245-1261
ISSN
  • 0890-9369 (ISSN-L)
  • 1549-5477
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
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

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