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

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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

DOI 10.4161/cc.10.15.16776PMC PMC3685613

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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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Authors: Witkiewicz, A. K., Knudsen, K. E., Dicker, A. P., & Knudsen, E. S.
Affiliations: Thomas Jefferson University (US)
Corresponding author: Knudsen, Erik S.
ORCID: Witkiewicz, Agnieszka K.
Knudsen, Karen E.
Dicker, Adam P.
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
DOI: 10.4161/cc.10.15.16776
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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The meaning of p16ink4aexpression in tumors: Functional significance, clinical associations and future developments

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