Lindstrom, L. | bioRxiv Science

bioRxiv2025

Decoding Cell Cycle Phase Variations in Cancer Hallmarks Across Breast Cancer Subgroups

Breast tumors have traditionally been categorized into four widely recognized subtypes. Recent single-cell advancements have, however, shown that individual tumors can contain more than one subtype, exhibiting their intrinsic heterogeneity. Relatedly, whilst the crucial role of cell cycle regulation in cancer development is widely acknowledged, the specific impact of cell cycle phases on oncogenic signaling and processes in each of these subtypes remains unresolved. Here, we examine the differences in transcriptomic cancer hallmarks across and within cell cycle phases and breast cancer subtypes in two large single-cell cohorts. We show that taking cell cycle phases into account identifies a broader pool of relevant cancer hallmark pathways while preserving the hallmarks found when cell cycle phases are ignored. Moreover, we identify FDA approved drugs that can target diverse hallmarks within specific phase-subtype cell combinations. This study highlights the critical role of cell cycle phases in advancing our understanding of breast cancer biology. The distinct biological mechanisms observed in each phase-subtype group suggest that targeting these hallmarks may provide a more precise and effective therapeutic strategy for breast cancer treatment.

bioinformatics↗

bioRxiv2017

Invasion triple trouble: Environmental fluctuations, fluctuation-adapted invaders and fluctuation-mal-adapted communities all govern invasion success

It has been suggested that climate change will lead to increased environmental fluctuations, which will undoubtedly have evolutionary consequences for all biota. For instance, fluctuations can directly increase the risk of invasions of alien species into new areas, as these species have repeatedly been proposed to benefit from disturbances. At the same time increased environmental fluctuations may also select for better invaders. However, selection by fluctuations may also influence the resistance of communities to invasions, which has rarely been tested. We tested eco-evolutionary dynamics of invasion with bacterial clones, evolved either in constant or fluctuating temperatures, and conducted experimental invasions in both conditions. We found clear evidence that ecological fluctuations, as well as adaptation to fluctuations by both the invader and community, all affected invasions, but played different roles at different stages of invasion. Ecological fluctuations clearly promoted invasions, especially into fluctuation mal-adapted communities. The evolutionary background of the invader clearly played a smaller role, and only at the later stages of invasion in the fluctuating environments. Our results indicate that climate change associated disturbances can directly increase the risk of invasions by altering ecological conditions during invasions, as well as via the evolution of both the invader and communities. Our experiment provides novel information on the complex consequences of climate change on invasions in general, and also charts risk factors associated with the spread of environmentally growing opportunistic pathogens.\n\nData AccessibilityUpon acceptance the data will be made publicly available.\n\nStatement of authorshipAuthors planned the questions and experiment together. KS conducted the laboratory work and wrote the first draft of the manuscript. TK conducted statistical analyses. All authors wrote the final version of the manuscript.

ecology↗