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The meaning of p16ink4aexpression in tumors: Functional significance, clinical associations and future developments
Open accessAbstract
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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“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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Metadata
- 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
- Publisher
- Informa UK Limited
- Published
- 2011-08
- Volume
- 10
- Issue
- 15
- Pages
- 2497-2503
- ISSN
- 1538-4101 (ISSN-L)
- 1551-4005
- PMC
- PMC3685613
- 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
- bronze
- doi.org
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › 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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