期刊
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
卷 370, 期 1673, 页码 -出版社
ROYAL SOC
DOI: 10.1098/rstb.2014.0219
关键词
complex multicellularity; cancer hallmarks; major transitions; microenvironment; division of labour; resource allocation
类别
资金
- US National Institutes of Health (NIH) [R01 CA170595, P01 CA91955, R01 CA149566, R01 CA185138, R01 CA140657]
- CDMRP Breast Cancer Research Program Award [BC132057]
- Sir John Templeton Foundation
- Agence National de la Recherche [ANR-13-BSV7-0003-01]
- ITMO Cancer [PC201306]
- National Science Foundation [DEB-0952260]
- Agence Nationale de la Recherche (ANR) [ANR-13-BSV7-0003] Funding Source: Agence Nationale de la Recherche (ANR)
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.
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