Int. J. Dev. Biol. In Press
doi: 10.1387/ijdb.210154av
© UPV/EHU Press

Promyelocytic Leukemia Protein (PML) and Stem Cells: from cancer to pluripotency

Amalia P. Vogiatzoglou1,2, Fabien Moretto2, Maria Makkou2, Joseph Papamatheakis1,2, Androniki Kretsovali*,2

1Department of Biology, University of Crete and 2Institute of Molecular Biology and Biotechnology (IMBB), Foundation for Research and Technology-Hellas (FORTH), Heraklion Crete, Greece

ABSTRACT The promyelocytic leukemia protein (PML) is the core organizer of the cognate nuclear bodies (PML-NBs). Through physical interaction or modification of diverse protein clients, PML-NBs regulate a multitude of - often antithetical- biological processes such as antiviral and stress response, inhibition of cell proliferation and autophagy, and promotion of apoptosis or senescence. Although PML was originally recognized as a tumor-suppressive factor, more recent studies revealed a “double faced” agent role for PML. Indeed PML displayed tumor cell pro-survival and pro-migratory functions via inhibition of migration suppressing molecules or promotion of transforming growth factor beta (TGF-β) mediated Epithelial-Mesenchymal Transition (EMT) that may promote cancer cell dissemination. In this line, PML was found to correlate with poor patient prognosis in distinct tumor contexts. Furthermore in the last decade, a number of publications have implicated PML in the physiology of normal or cancer stem cells (CSCs). Promyelocytic leukemia protein is activating fatty acid oxidation (FAO), a metabolic mechanism required for the asymmetric divisions and maintenance of hematopoietic stem cells (HSCs). In embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), PML is required for maintenance of the naïve and acquisition of the induced pluripotency state respectively. Correspondingly, PML ablation causes significant morphological, gene expression and lineage choice changes. In this review, we focus on the mechanisms orchestrated by PML and PML-NBs in cancer and healthy stem cells from cell physiology to the regulation of chromatin dynamics.

Keywords:

PML, stem cells, cancer, pluripotency, epigenetics

*Corresponding author e-mail: kretsova@imbb.forth.gr