MASTL: A novel therapeutic target for Cancer Malignancy

Abstract

Targeting mitotic kinases is an emerging anticancer approach with promising preclinical outcomes. Microtubule-associated serine/threonine kinase like (MASTL), also known as Greatwall (Gwl), is an important mitotic kinase that regulates mitotic progression of normal or transformed cells by blocking the activity of tumor suppressor protein phosphatase 2A (PP2A). MASTL upregulation has now been detected in multiple cancer types and associated with aggressive clinicopathological features. Apart, an aberrant MASTL activity has been implicated in oncogenic transformation through the development of chromosomal instability and alteration of key oncogenic signaling pathways. In this regard, recent publications have revealed potential role of MASTL in the regulation of AKT/mTOR and Wnt/β-catenin signaling pathways, which may be independent of its regulation of PP2A-B55 (PP2A holoenzyme containing a B55-family regulatory subunit). Taken together, MASTL kinase has emerged as a novel target for cancer therapeutics, and hence development of small molecule inhibitors of MASTL may significantly improve the clinical outcomes of cancer patients. In this article, we review the role of MASTL in cancer progression and the current gaps in this knowledge. We also discuss potential efficacy of MASTL expression for cancer diagnosis and therapy.