Within tumours, cancer cells are known to form genetically heterogeneous populations. However, there are also non-genetic factors, such as protein expression levels and metabolism, that contribute to cell heterogeneity and, consequently, cellular fitness. One way this non-genetic heterogeneity arises is from asymmetric mitosis (AM), where a mother cell produces two daughter cells with different characteristics. In this study (Buss et al., 2023), Guido Lenz and colleagues assess the contribution of AM to the generation of cellular fitness variability between sister cancer cells. Here, the authors find that sister cells generated from AM differ in their intermitotic time (IMT, used as a measure of fitness), as well as a number of morphological features. Mechanistically, the authors focus on the ERK pathway, which is implicated in cellular fitness. Here, the authors show that ERK activity in the mother cell prior to mitosis correlates negatively with the average IMT of the daughter cells. Significant differences in ERK activity between sister cells, however, was not observed until subsequent completions of the cell cycle, highlighting a temporal aspect of ERK activity. Furthermore, sister cells with the greatest differences in ERK activity also showed higher variability in IMT. Taken together, these data suggest that the cellular fitness of daughters arising from AM is influenced by ERK activity in the mother cell, thus demonstrating how AM can contribute to non-genetic heterogeneities in tumour cells.
