Multicellularity is characterized by cooperation among cells for the development, maintenance and reproduction of the multicellular organism. Cancer can be viewed as cheating within this cooperative ...multicellular system. Complex multicellularity, and the cooperation underlying it, has evolved independently multiple times. We review the existing literature on cancer and cancer-like phenomena across life, not only focusing on complex multicellularity but also reviewing cancer-like phenomena across the tree of life more broadly. We find that cancer is characterized by a breakdown of the central features of cooperation that characterize multicellularity, including cheating in proliferation inhibition, cell death, division of labour, resource allocation and extracellular environment maintenance (which we term the five foundations of multicellularity). Cheating on division of labour, exhibited by a lack of differentiation and disorganized cell masses, has been observed in all forms of multicellularity. This suggests that deregulation of differentiation is a fundamental and universal aspect of carcinogenesis that may be underappreciated in cancer biology. Understanding cancer as a breakdown of multicellular cooperation provides novel insights into cancer hallmarks and suggests a set of assays and biomarkers that can be applied across species and characterize the fundamental requirements for generating a cancer.
Microbes in the gastrointestinal tract are under selective pressure to manipulate host eating behavior to increase their fitness, sometimes at the expense of host fitness. Microbes may do this ...through two potential strategies: (i) generating cravings for foods that they specialize on or foods that suppress their competitors, or (ii) inducing dysphoria until we eat foods that enhance their fitness. We review several potential mechanisms for microbial control over eating behavior including microbial influence on reward and satiety pathways, production of toxins that alter mood, changes to receptors including taste receptors, and hijacking of the vagus nerve, the neural axis between the gut and the brain. We also review the evidence for alternative explanations for cravings and unhealthy eating behavior. Because microbiota are easily manipulatable by prebiotics, probiotics, antibiotics, fecal transplants, and dietary changes, altering our microbiota offers a tractable approach to otherwise intractable problems of obesity and unhealthy eating.
Nutrient competition affects all biological communities, including the human microbiota. Selection favors microbes that can influence their nutrient supply, potentially leading to microbial manipulation of human feeding behavior. Manipulation may involve neurochemical rewards, toxins, vagus nerve modulation, and manipulation of taste receptors, leading to cravings and unhealthy eating behavior.
Intratumor heterogeneity (ITH) drives neoplastic progression and therapeutic resistance. We used the bioinformatics tools 'expanding ploidy and allele frequency on nested subpopulations' (EXPANDS) ...and PyClone to detect clones that are present at a ≥10% frequency in 1,165 exome sequences from tumors in The Cancer Genome Atlas. 86% of tumors across 12 cancer types had at least two clones. ITH in the morphology of nuclei was associated with genetic ITH (Spearman's correlation coefficient, ρ = 0.24-0.41; P < 0.001). Mutation of a driver gene that typically appears in smaller clones was a survival risk factor (hazard ratio (HR) = 2.15, 95% confidence interval (CI): 1.71-2.69). The risk of mortality also increased when >2 clones coexisted in the same tumor sample (HR = 1.49, 95% CI: 1.20-1.87). In two independent data sets, copy-number alterations affecting either <25% or >75% of a tumor's genome predicted reduced risk (HR = 0.15, 95% CI: 0.08-0.29). Mortality risk also declined when >4 clones coexisted in the sample, suggesting a trade-off between the costs and benefits of genomic instability. ITH and genomic instability thus have the potential to be useful measures that can universally be applied to all cancers.
Abstract Laughter is a universally produced vocal signal that plays an important role in human social interaction. Researchers have distinguished between spontaneous and volitional laughter, but no ...empirical work has explored possible acoustic and perceptual differences. If spontaneous laughter is an honest signal of cooperative intent (e.g., derived from play breathing patterns), then the ability to mimic these sounds volitionally could have shaped perceptual systems to be attuned to aspects of spontaneous laughs that are harder to fake—features associated with phylogenetically older vocal control mechanisms. We extracted spontaneous laughs from conversations between friends and volitional laughs elicited by instruction without other provocation. In three perception experiments we found that, 1) participants could distinguish between spontaneous and volitional laughter, 2) when laugh speed was increased (duration decreased 33% and pitch held constant), all laughs were judged as more “real,” with judgment accuracy increasing for spontaneous laughter and decreasing for volitional laughter, and 3) when the laughs were slowed down (duration increased 260% and pitch altered proportionally), participants could not distinguish spontaneous laughs from nonhuman vocalizations but could identify volitional laughs as human-made. These findings and acoustic data suggest that spontaneous and volitional laughs are produced by different vocal systems, and that spontaneous laughter might share features with nonhuman animal vocalizations that volitional laughter does not.
Purpose of Review
We use an ecological lens to understand how microbes and cancer cells coevolve inside the ecosystems of our bodies. We describe how microbe-cancer cell interactions contribute to ...cancer progression, including cooperation between microbes and cancer cells. We discuss the role of the immune system in preventing this apparent ‘collusion’ and describe how microbe-cancer cell interactions lead to opportunities and challenges in treating cancer.
Recent Findings
Microbiota influence many aspects of our health including our cancer risk. Since both microbes and cancer cells rely on incoming resources for their survival and replication, excess energy and nutrient input from the host can play a role in cancer initiation and progression.
Summary
Certain microbes enhance cancer cell fitness by promoting proliferation and protecting cancer cells from the immune system. How diet influences these interactions remains largely unknown but recent evidence suggests a role for nutrients across the cancer continuum.
Life history trade-offs in cancer evolution Aktipis, C Athena; Boddy, Amy M; Gatenby, Robert A ...
Nature reviews. Cancer,
12/2013, Letnik:
13, Številka:
12
Journal Article
Recenzirano
Odprti dostop
Somatic evolution during cancer progression and therapy results in tumour cells that show a wide range of phenotypes, which include rapid proliferation and quiescence. Evolutionary life history ...theory may help us to understand the diversity of these phenotypes. Fast life history organisms reproduce rapidly, whereas those with slow life histories show less fecundity and invest more resources in survival. Life history theory also provides an evolutionary framework for phenotypic plasticity, which has potential implications for understanding 'cancer stem cells'. Life history theory suggests that different therapy dosing schedules might select for fast or slow life history cell phenotypes, with important clinical consequences.
Evolutionary foundations for cancer biology Aktipis, C. Athena; Nesse, Randolph M.
Evolutionary applications,
January 2013, 2013-Jan, 2013-01-00, 20130101, Letnik:
6, Številka:
1
Journal Article
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New applications of evolutionary biology are transforming our understanding of cancer. The articles in this special issue provide many specific examples, such as microorganisms inducing cancers, the ...significance of within‐tumor heterogeneity, and the possibility that lower dose chemotherapy may sometimes promote longer survival. Underlying these specific advances is a large‐scale transformation, as cancer research incorporates evolutionary methods into its toolkit, and asks new evolutionary questions about why we are vulnerable to cancer. Evolution explains why cancer exists at all, how neoplasms grow, why cancer is remarkably rare, and why it occurs despite powerful cancer suppression mechanisms. Cancer exists because of somatic selection; mutations in somatic cells result in some dividing faster than others, in some cases generating neoplasms. Neoplasms grow, or do not, in complex cellular ecosystems. Cancer is relatively rare because of natural selection; our genomes were derived disproportionally from individuals with effective mechanisms for suppressing cancer. Cancer occurs nonetheless for the same six evolutionary reasons that explain why we remain vulnerable to other diseases. These four principles—cancers evolve by somatic selection, neoplasms grow in complex ecosystems, natural selection has shaped powerful cancer defenses, and the limitations of those defenses have evolutionary explanations—provide a foundation for understanding, preventing, and treating cancer.
In times of crisis, risk pooling can enhance the resilience of individuals, households and communities. Risk-pooling systems are most effective when their participants adhere to several principles: ...(1) participants should agree that the pool is for needs that arise unpredictably, not for routine, predictable needs; (2) giving to those in need should not create an obligation for them to repay; (3) participants should not be expected to help others until they have taken care of their own needs; (4) participants should have a consensus about what constitutes need; (5) resources should be either naturally visible or made visible to reduce cheating; (6) individuals should be able to decide which partners to accept; and (7) the scale of the network should be large enough to cover the scale of risks. We discuss the cultural and evolutionary foundations of risk-pooling systems, their vulnerabilities and their relationship to commercial insurance.
Trichoplax adhaerens is the simplest multicellular animal with tissue differentiation and somatic cell turnover. Like all other multicellular organisms, it should be vulnerable to cancer, yet there ...have been no reports of cancer in T. adhaerens or any other placozoan. We investigated the cancer resistance of T. adhaerens, discovering that they are able to tolerate high levels of radiation damage (218.6 Gy). To investigate how T. adhaerens survive levels of radiation that are lethal to other animals, we examined gene expression after the X-ray exposure, finding overexpression of genes involved in DNA repair and apoptosis including the MDM2 gene. We also discovered that T. adhaerens extrudes clusters of inviable cells after X-ray exposure. T. adhaerens is a valuable model organism for studying the molecular, genetic, and tissue-level mechanisms underlying cancer suppression.
The capacity to innovate is often considered a defining feature of human societies, but it is not a capacity that is unique to human societies: innovation occurs in cellular societies as well. ...Cellular societies such as multicellular bodies and microbial communities, including the human microbiome, are capable of innovation in response to novel opportunities and threats. Multicellularity represents a suite of innovations for cellular cooperation, but multicellularity also opened up novel opportunities for cells to cheat, exploiting the infrastructure and resources of the body. Multicellular bodies evolve less quickly than the cells within them, leaving them vulnerable to cellular innovations that can lead to cancer and infections. In order to counter these threats, multicellular bodies deploy additional innovations including the adaptive immune system and the development of partnerships with preferred microbial partners. What can we learn from examining these innovations in cooperation and cheating in cellular societies? First, innovation in social systems involves a constant tension between novel mechanisms that enable greater size and complexity of cooperative entities and novel ways of cheating. Second, cultivating cooperation with partners who can rapidly and effectively innovate (such as microbes) is important for large entities including multicellular bodies. And third, multicellularity enabled cells to manage risk socially, allowing organisms to survive in challenging environments where life would otherwise be impossible. Throughout, we ask how insights from cellular societies might be translated into new innovations in human health and medicine, promoting and protecting the cellular cooperation that makes us viable multicellular organisms.
This article is part of the themed issue ‘Process and pattern in innovations from cells to societies’.
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