Abstract
Tumour evolution depends on heritable differences between cells in traits affecting cell survival or replication. It is well established that cancer cells are genetically and phenotypically heterogeneous; however, the extent to which this phenotypic variation is heritable is far less well explored. Here, we estimate the broad-sense heritability (H2) of two cell traits related to cancer hallmarks––cell motility and generation time––within populations of four cancer cell lines in vitro and find that motility is strongly heritable. This heritability is stable across multiple cell generations, with heritability values at the high end of those measured for a range of traits in natural populations of animals or plants. These findings confirm a central assumption of cancer evolution, provide a first quantification of the evolvability of key traits in cancer cells and indicate that there is ample raw material for experimental evolution in cancer cell lines. Generation time, a trait directly affecting cell fitness, shows substantially lower values of heritability than cell speed, consistent with its having been under directional selection removing heritable variation.
Highlights
Evolutionary processes are acknowledged to play a significant role in the initiation and progression of cancer, as well as in the acquisition of traits such as chemotherapy resistance [1,2,3]
Cancer evolution as a field rests on the reasonable, but rarely directly tested, assumption that a variety of cellular traits linked to cancer development and progression are heritable at the level of the cell population: that is, there is phenotypic variation between cancer cells, and that at least some of that variation is due to factors passed on from mother cell to daughter cell, rather than being caused by environmental factors such as nutrient availability
Heritability––which is defined in quantitative genetics as the proportion of trait variance in a population that is due to genetic variation, and which determines the response to selection [10]––has never been directly measured for any trait in cancer cell populations
Summary
Evolutionary processes are acknowledged to play a significant role in the initiation and progression of cancer, as well as in the acquisition of traits such as chemotherapy resistance [1,2,3]. Cancer evolution as a field rests on the reasonable, but rarely directly tested, assumption that a variety of cellular traits linked to cancer development and progression are heritable at the level of the cell population: that is, there is phenotypic variation between cancer cells, and that at least some of that variation is due to factors passed on from mother cell to daughter cell, rather than being caused by environmental factors such as nutrient availability. The heterogeneity of cancer cells, whether in tumours or laboratory cell lines, is well established––for instance, a recent multi-omics study found high levels of both genetic and phenotypic heterogeneity between different populations of HeLa cells [6]. Heritability––which is defined in quantitative genetics as the proportion of trait variance in a population that is due to genetic variation, and which determines the response to selection [10]––has never been directly measured for any trait in cancer cell populations
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