A Similar Speciation Process Relying on Cellular Stochasticity in Microbial and Cancer Cell Populations

Abstract

Summary Similarities between microbial and cancer cells were noticed in recent years and serve as a basis for an atavism theory of cancer. Cancer cells would rely on the reactivation of an ancestral “genetic program” that would have been repressed in metazoan cells. Here we argue that cancer cells resemble unicellular organisms mainly in their similar way to exploit cellular stochasticity to produce cell specialization and maximize proliferation. Indeed, the relationship between low stochasticity, specialization, and quiescence found in normal differentiated metazoan cells is lost in cancer. On the contrary, low stochasticity and specialization are associated with high proliferation among cancer cells, as it is observed for the “specialist” cells in microbial populations that fully exploit nutritional resources to maximize proliferation. Thus, we propose a model where the appearance of cancer phenotypes can be solely due to an adaptation and a speciation process based on initial increase in cellular stochasticity.

Tissue‐disruption‐induced cellular stochasticity and epigenetic drift: Common origins of aging and cancer?

“…This would correspond to a speciation process based on increased cellular stochasticity. [ 66 ] After initial perturbations producing such “uncontrolled” cells with high stochasticity, only some cancer cells would conserve the stem‐like state associated with low proliferation, whereas most of the cells would specialize and harbor decreased stochasticity associated with the optimal exploitation of nutritional resources and strong proliferation. [ 66 ]…”

Does Cancer Biology Rely on Parrondo’s Principles?

“…Indeed, recent single-cell analyses at the epigenomic level revealed no evidence that only highly unstable cells are present in advanced cancers; rather, cells with various levels of plasticity at various stages of tumor progression were found to co-exist [ 4 ]. These observations suggest that the co-existence of highly unstable and more stable subpopulations [ 5 , 9 ] should still be required for tumor maintenance and/or progression, even in advanced cancers. Furthermore, there is constant switch between the two states, as cells enriched for stem-like properties (i.e., unstable) known as tumor-initiating cells, can generate non-tumor-initiating cells, and the opposite [ 11 , 31 ], suggesting that the ability to change states (and the ratio between subpopulations expressing different states) is a necessary evolutionary strategy for tumor growth.…”

“…Such heterogeneity allows populations to survive in fluctuating environments and promotes interactions among distinct phenotypic subpopulations leading to cell specialization (e.g., [ 8 ]). We have previously discussed the parallel between cancer cells and microbial populations from the point of view of cellular stochasticity (related to gene expression variability) and the way such stochasticity can be exploited to produce subpopulations better adapted to a given environment [ 9 ]. Specifically, we proposed that oncogenic processes rely on the initial increase in cellular stochasticity associated with cell de-differentiation, followed by the specialization of some cancer sub-populations while maintaining a less specialized lineage (cancer stem cells) with high stochasticity levels [ 9 ].…”

“…We have previously discussed the parallel between cancer cells and microbial populations from the point of view of cellular stochasticity (related to gene expression variability) and the way such stochasticity can be exploited to produce subpopulations better adapted to a given environment [ 9 ]. Specifically, we proposed that oncogenic processes rely on the initial increase in cellular stochasticity associated with cell de-differentiation, followed by the specialization of some cancer sub-populations while maintaining a less specialized lineage (cancer stem cells) with high stochasticity levels [ 9 ]. This can explain the co-existence of less specialized cells with higher stochasticity at the epigenetic and transcriptional levels able to diversify into many phenotypes, and more specialized cells with more stable epigenetic and transcriptional profiles that maximize exploitation of available resources in the surrounding environment.…”

The Genomic Processes of Biological Invasions: From Invasive Species to Cancer Metastases and Back Again

“…In the context of biodiversity and ecology, microbial, plant, and animal species invade non-native ecosystems imposing ecological and economic problems and challenges on a global scale (Pimentel et al, 2000;Pyšek and Richardson, 2010;Simberloff et al, 2013;Strong and Ayres, 2013;van Kleunen et al, 2018;Bartz and Kowarik, 2019;Cuthbertab et al, 2021). In cancers, a primary tumor in one tissue can give rise to lineages that disperse to a wide variety of novel environments in other tissues of the host (Turajlic et al, 2018;Capp and Thomas, 2020), imposing a potentially lethal cost on the host (Pienta et al, 2020a;Dujon et al, 2021). Evolutionary processes are inherent to invasions as biological entities are exposed to environmental conditions that may vary from their original environments.…”