Cited by 287Cancer-related Molecular PathwaysTelomeres, Telomerase, and SenescencePI3K/AKT/mTOR signaling in cancer

The meaning of p16ink4aexpression in tumors: Functional significance, clinical associations and future developments

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Witkiewicz, Agnieszka K., Knudsen, Karen E., Dicker, Adam P., Knudsen, Erik S.·2011·Cell Cycle

Abstract

The CDKN2A gene is a tumor suppressor that encodes the CDK4/6 inhibitor p16(ink4a). Loss of this tumor suppressor contributes to the bypass of critical senescent signals and is associated with progression to malignant disease. However, the high-level expression of p16(ink4a) in tumors is associated with aggressive subtypes of disease, and in certain clinical settings elevated p16(ink4a) expression is an important determinant for disease prognosis and therapeutic response. These seemingly contradictory facets of p16(ink4a) expression have lead to confusion related to the meaning of this tumor suppression in tumor pathobiology. As reviewed here, the alternative expression of p16(ink4a) represents an ideal marker for considering RB-pathway function, tumor heterogeneity, and novel means for directing therapy.

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  • Mutations, silencing, or loss of CDKN2A facilitate senescence bypass and are frequently associated with carcinogenesis.

    “In agreement with p16's role as a guardian of senescence, mutations, silencing or loss of CDKN2A, the gene encoding p16, facilitate senescence bypass and it is frequently associated with carcinogenesis (reviewed in.51,52”

    From Senescence from G2 arrest, revisited (2015) · cites this paper as [52]

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Authors
Witkiewicz, A. K., Knudsen, K. E., Dicker, A. P., & Knudsen, E. S.
Affiliations
Thomas Jefferson University (US)
Corresponding author
Knudsen, Erik S.
Venue
Cell Cycle
Published
2011-08
Volume
10
Issue
15
Pages
2497-2503
ISSN
  • 1538-4101 (ISSN-L)
  • 1551-4005
OpenAlex
W2019517928
Cited by
286
References
62
Citations by year
2026: 14 · 2025: 22 · 2024: 14 · 2023: 22 · 2022: 29 · 2021: 16 · 2020: 26 · 2019: 26 · 2018: 24 · 2017: 18 · 2016: 13 · 2015: 19 · 2014: 14 · 2013: 19 · 2012: 10
FWCI
1.26
Type
journal article
Language
en
Open access
Locations
  • Cell Cycle (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Cancer Institute (R01CA099996)
Topics
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
  • Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
Keywords
p16INK4a, CDKN2A, tumor suppressor, Rb pathway, cellular senescence, tumor heterogeneity, prognosis, treatment response, tumor progression, CDK4/6 inhibition
MeSH terms
Humans, Neoplasms, Gene Expression Regulation, Neoplastic, Retinoblastoma Protein, Cyclin-Dependent Kinase Inhibitor p16, Cyclin-Dependent Kinase 4, Cyclin-Dependent Kinase 6, Cyclin D

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