Polyploidy and mTOR signaling: a possible molecular link

Abstract

AbstractPolyploidy is typically described as the condition wherein a cell or organism has more than two complete sets of chromosomes. Occurrence of polyploidy is a naturally occurring phenomenon in the body’s development and differentiation processes under normal physiological conditions. However, in pathological conditions, the occurrence of polyploidy is documented in numerous disorders, including cancer, aging and diabetes. Due to the frequent association that the polyploidy has with these pathologies and physiological process, understanding the cause and consequences of polyploidy would be beneficial to develop potential therapeutic applications. Many of the genetic and epigenetic alterations leading to cancer, diabetes and aging are linked to signaling pathways. Nonetheless, the specific signaling pathway associated with the cause and consequences of polyploidy still remains largely unknown. Mammalian/mechanistic target of rapamycin (mTOR) plays a key role in the coordination between eukaryotic cell growth and metabolism, thereby simultaneously respond to various environmental inputs including nutrients and growth factors. Extensive research over the past two decades has established a central role for mTOR in the regulation of many fundamental cellular processes that range from protein synthesis to autophagy. Dysregulated mTOR signaling has been found to be implicated in various disease progressions. Importantly, there is a strong correlation between the hallmarks of polyploidy and dysregulated mTOR signaling. In this review, we explore and discuss the molecular connection between mTOR signaling and polyploidy along with its association with cancer, diabetes and aging. Additionally, we address some unanswered questions and provide recommendations to further advance our understanding of the intricate relationship between mTOR signaling and polyploidy.