Abstract
Dormancy is a key survival strategy in many organisms across the tree of life. Organisms that utilize some type of dormancy (hibernation, aestivation, brumation, diapause, and quiescence) are able to survive in habitats that would otherwise be uninhabitable. Induction into dormant states is typically caused by environmental stress. While organisms are dormant, their physical activity is minimal, and their metabolic rates are severely depressed (hypometabolism). These metabolic reductions allow for the conservation and distribution of energy while conditions in the environment are poor. When conditions are more favorable, the organisms are then able to come out of dormancy and reengage in their environment. Polyaneuploid cancer cells (PACCs), proposed mediators of cancer metastasis and resistance, access evolutionary programs and employ dormancy as a survival mechanism in response to stress. Quiescence, the type of dormancy observed in PACCs, allows these cells the ability to survive stressful conditions (e.g., hypoxia in the microenvironment, transiting the bloodstream during metastasis, and exposure to chemotherapy) by downregulating and altering metabolic function, but then increasing metabolic activities again once stress has passed. We can gain insights regarding the mechanisms underlying PACC dormancy by looking to the evolution of dormancy in different organisms.
Highlights
DORMANCY, AND CANCERMetastatic cancer is resistant to almost all known systemic therapies and remains largely incurable (Pienta et al, 2020b)
This review focuses on what we can learn from dormancy observed in ecology to better understand how polyaneuploid cancer cells alter their metabolism and survive in a dormant state while under stress
Cancer cells undergoing stress such as starvation, radiation, or chemotherapy are known to have an altered metabolism compared to their non-stress counterparts, with evidence of accumulation of lipids and an increase in autophagy to survive (Hanahan and Weinberg, 2011)
Summary
Metastatic cancer is resistant to almost all known systemic therapies and remains largely incurable (Pienta et al, 2020b). There are many different forms of dormancy including hibernation (winter dormancy) (Geiser, 2013), aestivation (summer or dry season dormancy) (Storey and Storey, 2012), brumation (winter dormancy observed in ectotherms) (Wilkinson et al, 2017), diapause (period of suspended development in an insect, invertebrate, or mammal embryo in unfavorable conditions) (Denlinger, 2000; Tougeron, 2019), and quiescence (opportunistic inactivity observed in plants and cells) (Table 1) (Navas and Carvalho, 2010) During all of these dormant conditions organisms alter their metabolism to better survive unfavorable circumstances in their environment. Saccharomyces cerevisiae provide a unique model that can be used to better understand cancer cell metabolism during dormancy
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