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Cited by 23Kruppel-like factors researchTelomeres, Telomerase, and SenescenceGenetics, Aging, and Longevity in Model Organisms

Krüppel-Like Factor 6 Is Required for Oxidative and Oncogene-Induced Cellular Senescence

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Sabatino, Maria Eugenia, Castellaro, Andrés, Racca, Ana C., Carbajosa González, Sofía, Pansa, Maria Florencia, Soria, Gastón, Bocco, Jose Luis·2019·Frontiers in Cell and Developmental Biology
DOI 10.3389/fcell.2019.00297PMC PMC6882731
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Abstract

KLF6 is a transcription factor involved in the regulation of several cellular processes. Regarding its role in tumorigenesis, KLF6 is considered a tumor suppressor. Numerous reports demonstrate its frequent genomic loss or down-regulation, implying a functional inactivation in a broad range of human cancers. Previous work from our laboratory showed that the down-regulation of KLF6 expression in normal fibroblasts leads to cellular transformation, while its ectopic expression interferes with the oncogenic transformation triggered by activated Ras through a cell cycle arrest. We hypothesize that the growth suppressor activity of KLF6 may involve the induction of cellular senescence thereby helping to prevent the proliferation of cells at risk of neoplastic transformation. Here, we explored the association of KLF6 up-regulation in two different cellular senescence scenarios. We found that KLF6 silencing bypasses both oxidative and oncogene-induced senescence. In this context, KLF6 expression per se was capable to trigger cellular senescence in both normal and tumoral contexts. As such, the findings presented in this report provide insights into a potential mechanism by which KLF6 may play a suppressing role of uncontrolled or damaged cell proliferation.

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  • KLF6 and ATF3 are implicated in p21 regulation and senescence establishment.

    “as well as KLF6 and ATF3, both implicated in p21 regulation and senescence establishment.61,62,63”

    From Cellular senescence in human liver under normal aging and cancer (2026) · cites this paper as [62]

  • Genes upregulated in at least three senescent populations included NFKB1, KLF6, and ATF3.

    “These included the previously discussed TF NFKB1, known for SASP regulation, as well as KLF6 and ATF3, both implicated in p21 regulation and senescence establishment.61,62,63”

    From Cellular senescence in human liver under normal aging and cancer (2026) · cites this paper as [62]

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References 68 · Cited by 23

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Authors
Sabatino, M. E., Castellaro, A., Racca, A. C., Carbajosa González, S., Pansa, M. F., Soria, G., & Bocco, J. L.
Affiliations
Consejo Nacional de Investigaciones Científicas y Técnicas (AR)
ORCID
Venue
Frontiers in Cell and Developmental Biology
Publisher
Frontiers Media SA
Published
2019-11-22
Volume
7
Pages
297-297
ISSN
2296-634X (ISSN-L)
DOI
10.3389/fcell.2019.00297
PMC
PMC6882731
OpenAlex
W2991591952
Cited by
23
References
68
Citations by year
2026: 5 · 2025: 6 · 2024: 5 · 2023: 1 · 2022: 1 · 2021: 3 · 2020: 2
FWCI
0.50
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Cell and Developmental Biology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by-nc-sa)
Funders
  • Consejo Nacional de Investigaciones Científicas y Técnicas
  • Agencia Nacional de Promoción Científica y Tecnológica
  • Secretaria de Ciencia y Tecnología - Universidad Nacional de Córdoba
  • Instituto Nacional del Cáncer
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Kruppel-like factors research
  • Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
Keywords
KLF6, cellular senescence, oxidative stress, oncogene-induced senescence, tumor suppressor, transcription factors, cell cycle arrest, fibroblasts, carcinogenesis, growth inhibition

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