Variation in the life history strategy of cells underlies tumor’s functional diversity

Classical r- vs. K-selection theory describes the trade-offs between high reproductive output and competitiveness and guides research in evolutionary ecology1-5. While its impact has waned in the recent past, cancer evolution may rekindle it6-10. Indeed, solid tumors are an ideal theater for r- and K-selection and, hence, a good testing ground for ideas on life-history strategy evolution11,12. In this study, we impose r- or K-selection on HeLa cells to obtain strongly proliferative r cells and highly competitive K cells. RNA-seq analysis indicates that phenotypic trade-offs in r and K cells are associated with distinct patterns of expression of genes involved in the cell cycle, adhesion, apoptosis, and contact inhibition. Both empirical observations and simulations based on an ecological competition model show that the trade-off between cell proliferation and competitiveness can evolve adaptively and rapidly in naive cell lines. It is conceivable that the contrasting selective pressure may operate in a realistic ecological setting of actual tumors. When the r and K cells are mixed in vitro, they exhibit strikingly different spatial and temporal distributions in the resultant cultures. Thanks to this niche separation, the fitness of the entire tumor increases. Our analyses of life-history trade-offs are pertinent to evolutionary ecology as well as cancer biology.