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Genetic Alterations in the INK4a/ARF Locus: Effects on Melanoma Development and Progression
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Non-Canonical Functions of the ARF Tumor Suppressor in Development and Tumorigenesis

1
Molecular Carcinogenesis Group, Department of Histology and Embryology, School of Medicine, National Kapodistrian University of Athens (NKUA), 115 27 Athens, Greece
2
Biomedical Research Foundation, Academy of Athens, 106 79 Athens, Greece
3
Molecular and Clinical Cancer Sciences, Manchester Cancer Research Centre, Manchester Academic Health Sciences Centre, University of Manchester, Manchester M13 9PR, UK
4
Center for New Biotechnologies and Precision Medicine, Medical School, National and Kapodistrian University of Athens, 115 27 Athens, Greece
*
Authors to whom correspondence should be addressed.
Biomolecules 2021, 11(1), 86; https://doi.org/10.3390/biom11010086
Received: 1 December 2020 / Revised: 2 January 2021 / Accepted: 4 January 2021 / Published: 12 January 2021
(This article belongs to the Special Issue Deciphering alternative functions of the INK4a/ARF locus)
P14ARF (ARF; Alternative Reading Frame) is an extensively characterized tumor suppressor which, in response to oncogenic stimuli, mediates cell cycle arrest and apoptosis via p53-dependent and independent routes. ARF has been shown to be frequently lost through CpG island promoter methylation in a wide spectrum of human malignancies, such as colorectal, prostate, breast, and gastric cancers, while point mutations and deletions in the p14ARF locus have been linked with various forms of melanomas and glioblastomas. Although ARF has been mostly studied in the context of tumorigenesis, it has been also implicated in purely developmental processes, such as spermatogenesis, and mammary gland and ocular development, while it has been additionally involved in the regulation of angiogenesis. Moreover, ARF has been found to hold important roles in stem cell self-renewal and differentiation. As is often the case with tumor suppressors, ARF functions as a pleiotropic protein regulating a number of different mechanisms at the crossroad of development and tumorigenesis. Here, we provide an overview of the non-canonical functions of ARF in cancer and developmental biology, by dissecting the crosstalk of ARF signaling with key oncogenic and developmental pathways. View Full-Text
Keywords: ARF; tumor suppressor; non-canonical functions; cancer biology; developmental biology; Hippo pathway; Wnt pathway; Notch pathway ARF; tumor suppressor; non-canonical functions; cancer biology; developmental biology; Hippo pathway; Wnt pathway; Notch pathway
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MDPI and ACS Style

Lagopati, N.; Belogiannis, K.; Angelopoulou, A.; Papaspyropoulos, A.; Gorgoulis, V. Non-Canonical Functions of the ARF Tumor Suppressor in Development and Tumorigenesis. Biomolecules 2021, 11, 86. https://doi.org/10.3390/biom11010086

AMA Style

Lagopati N, Belogiannis K, Angelopoulou A, Papaspyropoulos A, Gorgoulis V. Non-Canonical Functions of the ARF Tumor Suppressor in Development and Tumorigenesis. Biomolecules. 2021; 11(1):86. https://doi.org/10.3390/biom11010086

Chicago/Turabian Style

Lagopati, Nefeli; Belogiannis, Konstantinos; Angelopoulou, Andriani; Papaspyropoulos, Angelos; Gorgoulis, Vassilis. 2021. "Non-Canonical Functions of the ARF Tumor Suppressor in Development and Tumorigenesis" Biomolecules 11, no. 1: 86. https://doi.org/10.3390/biom11010086

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