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Philos Trans R Soc Lond B Biol Sci. 2015 Jul 19;370(1673). pii: 20140219. doi: 10.1098/rstb.2014.0219.

Cancer across the tree of life: cooperation and cheating in multicellularity.

Author information

1
Center for Evolution and Cancer, University of California San Francisco, San Francisco, CA 94143, USA Department of Psychology, Arizona State University, Tempe, AZ 85287-4501, USA Centre for Evolution and Cancer, Institute for Cancer Research, 123 Old Brompton Road, London SW7 3RP, UK Institute for Advanced Study, Wissenschaftskolleg zu Berlin, Berlin, Germany aktipis@asu.edu.
2
Center for Evolution and Cancer, University of California San Francisco, San Francisco, CA 94143, USA Department of Psychology, Arizona State University, Tempe, AZ 85287-4501, USA Institute for Advanced Study, Wissenschaftskolleg zu Berlin, Berlin, Germany.
3
Department of Evolutionary Ecology and Genetics, University of Kiel, Am Botanischen Garten 1-9, 24118 Kiel, Germany Institute for Advanced Study, Wissenschaftskolleg zu Berlin, Berlin, Germany.
4
CNRS, UMR 5535, Institut de Génétique Moléculaire de Montpellier, Université de Montpellier, Montpellier, France Institute for Advanced Study, Wissenschaftskolleg zu Berlin, Berlin, Germany.
5
Institut des Sciences de l'Evolution, CNRS UMR5554, Université Montpellier, 34095 Montpellier, France Santa Fe Institute, 1399 Hyde Park Road, Santa Fe, NM 87501, USA Institute for Advanced Study, Wissenschaftskolleg zu Berlin, Berlin, Germany.
6
Center for Evolution and Cancer, University of California San Francisco, San Francisco, CA 94143, USA Centre for Evolution and Cancer, Institute for Cancer Research, 123 Old Brompton Road, London SW7 3RP, UK Biodesign Institute, School of Life Sciences, Arizona State University, PO Box 8724501, Tempe, AZ 85287-4501, USA Institute for Advanced Study, Wissenschaftskolleg zu Berlin, Berlin, Germany.
7
Department of Biology, University of Maryland, College Park, MD 20742, USA Institute for Advanced Study, Wissenschaftskolleg zu Berlin, Berlin, Germany.

Abstract

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.

KEYWORDS:

cancer hallmarks; complex multicellularity; division of labour; major transitions; microenvironment; resource allocation

PMID:
26056363
PMCID:
PMC4581024
DOI:
10.1098/rstb.2014.0219
[Indexed for MEDLINE]
Free PMC Article

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