Cited by 337Cancer-related Molecular PathwaysPI3K/AKT/mTOR signaling in cancerUbiquitin and proteasome pathways

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p21 in Cancer Research

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Shamloo, Bahar, Usluer, Sinem·2019·Cancers

DOI 10.3390/cancers11081178PMC PMC6721478

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Abstract

p21 functions as a cell cycle inhibitor and anti-proliferative effector in normal cells, and is dysregulated in some cancers. Earlier observations on p21 knockout models emphasized the role of this protein in cell cycle arrest under the p53 transcription factor activity. Although tumor-suppressor function of p21 is the most studied aspect of this protein in cancer, the role of p21 in phenotypic plasticity and its oncogenic/anti-apoptotic function, depending on p21 subcellular localization and p53 status, have been under scrutiny recently. Basic science and translational studies use precision gene editing to manipulate p21 itself, and proteins that interact with it; these studies have led to regulatory/functional/drug sensitivity discoveries as well as therapeutic approaches in cancer field. In this review, we will focus on targeting p21 in cancer research and its potential in providing novel therapies.

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Figure 1 p21 expression induction through PI3K-Akt and c-Myc pathways. In this figure, drugs are shown in green boxes and differentially expressed genes/miRNAs are shown in pink boxes. These differentially expressed genes/miRNAs and drugs positively regulate p21 expression through reducing Akt phosphorylation, inhibiting MDM2-p53 interaction, suppressing c-Myc expression, preventing p21 ubiquitylation, preventing p21 mRNA destabilization, blocking negative regulation of p21 protein, or suppressing histone deacetylation. As a conclusion, increased p21 expression induces cell cycle arrest and decreases cell viability. PI3K: Phosphoinositide 3-Kinase, Akt: Protein kinase B, ARHGAP15: Rho GTPase-Activating Protein 15, ARHGAP17: Rho GTPase Activating Protein 17, c-MYC: cellular Myelocytomatosis Oncogene, CMTM5: CKLF (Chemokine Like Factor) Like MARVEL Transmembrane Domain Containing 5, FBXO22: F-box Only Protein 22, FXR1: Fragile X-related Protein 1, GSTP1: Glutathione S-Transferase Pi 1, HDAC: Histone Deacetylase, hnRNP A2/B1: Heterogeneous Nuclear Ribonucleoprotein A2/B1, IL-6: Interleukin 6, LRH-1: Nuclear Receptor Liver Receptor Homolog-1, MAPKAPK5-AS1: MAPKAPK5 Antisense RNA 1, MDM2: Mouse Double Minute 2, mTOR: Mammalian Target of Rapamycin, PI3K: Phosphoinositide-3-Kinase, PSMD2: 26S Proteasome non-ATPase Regulatory Subunit 2, UBR5: Ubiquitin Protein Ligase E3 Component N-Recognin 5.CC BY · PubMed Central

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Authors: Shamloo, B., & Usluer, S.
Affiliations: University of Utah (US)
Medical University of Graz (AT)
Corresponding author: Shamloo, Bahar
ORCID: Shamloo, Bahar
Usluer, Sinem
Venue: Cancers
Publisher: MDPI AG
Published: 2019-08-14
Volume: 11
Issue: 8
Pages: 1178
ISSN: 2072-6694 (ISSN-L)
DOI: 10.3390/cancers11081178
PMC: PMC6721478
OpenAlex: W2968190332
Cited by: 336
References: 175
Citations by year: 2026: 18 · 2025: 47 · 2024: 63 · 2023: 65 · 2022: 52 · 2021: 56 · 2020: 31 · 2019: 3
FWCI: 3.41
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
Locations: Cancers (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics: Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
Keywords: p21, cell cycle inhibitors, p53, tumor suppression, phenotypic plasticity, oncogenic function, anti-apoptotic effects, subcellular localization, genome editing, cancer therapy, drug sensitivity

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