Cooperation of partially-transformed clones: an invisible force behind the early stages of carcinogenesis.
Royal Society open science
The Royal Society
MetadataShow full item record
Esposito, A. (2021). Cooperation of partially-transformed clones: an invisible force behind the early stages of carcinogenesis.. Royal Society open science, 8 (2)https://doi.org/10.1098/rsos.201532
Most tumours exhibit significant heterogeneity and are best described as communities of cellular populations competing for resources. Growing experimental evidence also suggests, however, that cooperation between cancer clones is important as well for the maintenance of tumour heterogeneity and tumour progression. However, a role for cell communication during the earliest steps in oncogenesis is not well characterised despite its vital importance in normal tissue and clinically manifest tumours. Here, we present a simple analytical model and stochastic lattice-based simulations to study how the interaction between the mutational process and cell-to-cell communication in three-dimensional tissue architecture might contribute to shape early oncogenesis. We show that non-cell-autonomous mechanisms of carcinogenesis could support and accelerate pre-cancerous clonal expansion through the cooperation of different, non- or partially- transformed mutants. We predict the existence of a ‘cell-autonomous time-horizon’, a time before which cooperation between cell-to-cell communication and DNA mutations might be one of the most fundamental forces shaping the early stages of oncogenesis. The understanding of this process could shed new light on the mechanisms leading to clinically manifest cancers.
“Alessandro Esposito acknowledges the financial support provided by the CRUK with a multi-disciplinary project award (OncoLive, NS/A000077/1), pump-priming funds from the CRUK Cambridge Institute. Alessandro Esposito also acknowledges financial support from Medical Research Council program grants (MC_UU_12022/1 and MC_UU_12022/8) awarded to Prof. Ashok Venkitaraman
Cancer Research UK (C54674/A27487)
Medical Research Council (MC_UU_12022/1)
Embargo Lift Date
External DOI: https://doi.org/10.1098/rsos.201532
This record's URL: https://www.repository.cam.ac.uk/handle/1810/316685
Licence URL: https://creativecommons.org/licenses/by/4.0/