PML tumour suppression and beyond: therapeutic implications

Cristina Gamell, Piotr Jan Paul, Ygal Haupt, Sue Haupt

Research output: Contribution to journalArticleResearchpeer-review

14 Citations (Scopus)

Abstract

Recognition of the tumour suppressive capacity of the Promyelocytic Leukemia protein (PML) has emerged beyond its identification through APL, to a broad spectrum of tumors. This ability has chiefly been linked to its role as a core component of dynamic structures termed PML Nuclear Bodies (PML-NBs). In response to a variety of stresses, key factors and their molecular modifiers are recruited to PML-NBs, where activating modifications are facilitated, leading to a cellular stress response. PML was also found to perform anti-tumourigenic functions through cytoplasmic activities. Surprisingly, important recent research defined growth promoting capabilities of PML, which significantly challenges the notion of a classic tumour suppressor. Through metabolic reprogramming, PML can afford a selective advantage for tumor cells in certain settings. The multiple forms in which PML exists are the likely explanation of this functional diversity. This behavioral ambiguity however raises a significant challenge to the design of strategies to therapeutically target PML. In this review we discuss this change of paradigm in the PML field and its ramifications, particularly for tailoring cancer therapies.
Original languageEnglish
Pages (from-to)2653 - 2662
Number of pages10
JournalFEBS Letters
Volume588
Issue number16
DOIs
Publication statusPublished - 2014

Cite this