Περίληψη:
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. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
Συγγραφείς:
Lagopati, N.
Belogiannis, K.
Angelopoulou, A.
Papaspyropoulos, A.
Gorgoulis, V.
Λέξεις-κλειδιά:
adenosine diphosphate ribosylation factor; cyclin dependent kinase inhibitor 2A; forkhead box protein M1; microRNA; platelet derived growth factor; polycomb repressive complex 2; protein p53; Ras association domain family protein 1A; vasculotropin A; cyclin dependent kinase inhibitor 2A, apoptosis; carcinogenesis; cell cycle arrest; cell differentiation; cell maturation; CpG island; developmental biology; down regulation; epithelial mesenchymal transition; gene expression; gene knockout; gene mutation; genomic instability; hippo signaling; human; induced pluripotent stem cell; morphogenesis; Notch signaling; organogenesis; point mutation; promoter region; Review; signal transduction; stem cell self-renewal; tissue regeneration; tumor growth; tumor microenvironment; tumor suppressor gene; tumor volume; upregulation; Wnt signaling; animal; carcinogenesis; embryo development; metabolism; pathology; stem cell, Animals; Carcinogenesis; Embryonic Development; Genes, Tumor Suppressor; Humans; Signal Transduction; Stem Cells; Tumor Suppressor Protein p14ARF