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Open AccessJournal ArticleDOI

The Multifaceted p21 (Cip1/Waf1/CDKN1A) in Cell Differentiation, Migration and Cancer Therapy

Nina-Naomi Kreis, +2 more
- 21 Aug 2019 - 
- Vol. 11, Iss: 9, pp 1220
TLDR
The protein p21 is the founding member of cyclin-dependent kinase inhibitors and an important versatile cell cycle protein that acts either as a tumor suppressor or as an oncogene depending largely on the cellular context, its subcellular localization and posttranslational modifications.
Abstract
Loss of cell cycle control is characteristic of tumorigenesis. The protein p21 is the founding member of cyclin-dependent kinase inhibitors and an important versatile cell cycle protein. p21 is transcriptionally controlled by p53 and p53-independent pathways. Its expression is increased in response to various intra- and extracellular stimuli to arrest the cell cycle ensuring genomic stability. Apart from its roles in cell cycle regulation including mitosis, p21 is involved in differentiation, cell migration, cytoskeletal dynamics, apoptosis, transcription, DNA repair, reprogramming of induced pluripotent stem cells, autophagy and the onset of senescence. p21 acts either as a tumor suppressor or as an oncogene depending largely on the cellular context, its subcellular localization and posttranslational modifications. In the present review, we briefly mention the general functions of p21 and summarize its roles in differentiation, migration and invasion in detail. Finally, regarding its dual role as tumor suppressor and oncogene, we highlight the potential, difficulties and risks of using p21 as a biomarker as well as a therapeutic target.

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Citations
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Journal ArticleDOI

Role of p53 in the Regulation of Cellular Senescence

TL;DR: The p53-mediated regulation of several pathophysiological microenvironments that could be associated with senescence and its development are discussed, including the surrounding tissue microenvironment and the neighboring cells by secreting pro-inflammatory cytokines.
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Glioma: molecular signature and crossroads with tumor microenvironment.

TL;DR: In this paper, the authors provide an update about these junctions where constant traffic of biomolecules adds complexity in the management of glioblastoma, and identify and characterise these complex mechanisms are inevitably necessary to adapt therapeutic strategies and to develop novel measures.
Journal ArticleDOI

Endothelial sprouting, proliferation, or senescence: tipping the balance from physiology to pathology

TL;DR: The main findings on the mechanisms controlling physiological vascular sprouting, proliferation, and senescence are reviewed and how those mechanisms are often deregulated in acquired or congenital cardiovascular disease leading to a diverse range of pathologies are reviewed.
References
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Journal ArticleDOI

WAF1, a potential mediator of p53 tumor suppression

TL;DR: A gene is identified, named WAF1, whose induction was associated with wild-type but not mutant p53 gene expression in a human brain tumor cell line and that could be an important mediator of p53-dependent tumor growth suppression.
Journal ArticleDOI

The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases

TL;DR: In this article, an improved two-hybrid system was employed to isolate human genes encoding Cdk-interacting proteins (Cips) and found that CIP1 is a potent, tight-binding inhibitor of Cdks and can inhibit the phosphorylation of Rb by cyclin A-Cdk2.
Journal ArticleDOI

The limited in vitro lifetime of human diploid cell strains

TL;DR: The survival curves obtained with human diploid cell strains are comparable to “multiple-hit” or “ multiple-target” curves obtain with other biological systems where an initial threshold dose is required before an exponential form of the curve is established.
Journal ArticleDOI

Cell migration: integrating signals from front to back.

TL;DR: The mechanisms underlying the major steps of migration and the signaling pathways that regulate them are described, and recent advances investigating the nature of polarity in migrating cells and the pathways that establish it are outlined.
Journal ArticleDOI

A Perspective on Cancer Cell Metastasis

TL;DR: It is suggested that metastasis can be portrayed as a two-phase process: the first phase involves the physical translocation of a cancer cell to a distant organ, whereas the second encompasses the ability of the cancer cellto develop into a metastatic lesion at that distant site.
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