title: Dispersal evolution in neoplasms: the role of disregulated metabolism in the evolution of cell motility.
abstract: Here, we apply the theoretical framework of dispersal evolution to understand the emergence of invasive and metastatic cells. We investigate whether the dysregulated metabolism characteristic of cancer cells may play a causal role in selection for cell motility, and thus to the tissue invasion and metastasis that define cancer. With an agent-based computational model, we show that cells with higher metabolism evolve to have higher rates of movement and that "neoplastic" cells with higher metabolism rates are able to persist in a population of "normal" cells with low metabolic rates, but only if increased metabolism is accompanied by increased motility. This is true even when the cost of motility is high. These findings suggest that higher rates of cell metabolism lead to selection for motile cells in premalignant neoplasms, which may preadapt cells for subsequent invasion and metastasis. This has important implications for understanding the progression of cancer from less invasive to more invasive cell types.
authors.affiliation: Department of Ecology and Evolutionary Biology, University of Arizona, P.O. Box 210088, Tucson, Arizona 85721, USA. aktipis@alumni.reed.edu
authors.forename: C Athena
authors.initials: CA
authors.lastname: Aktipis
authors.forename: Carlo C
authors.initials: CC
authors.lastname: Maley
authors.forename: John W
authors.initials: JW
authors.lastname: Pepper
mesh_terms: D005075:Biological Evolution; D002465:Cell Movement / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D014407:Tumor Cells, Cultured; D059016:Tumor Microenvironment