Bioinformatics Seminar
Time:
Venue: Na
14 June 2016
NaHow does the evolutionary history of cellular networks set the stage for cancer?
Anna TrigosPeter Mac
The network of interactions between genes and proteins provides both the constraints and the plasticity that allows the convergence to the hallmarks of cancer in tumours of diverse genetic makeup. Network regions shaped during distinct evolutionary time periods can be associated with tumourigenesis ; with tumours relying on cellular processes that date back to unicellular ancestors (e.g. ; cell replication ; glycolysis) ; and deregulating key pathways of the emergence of multicellularity. We hypothesized that phenotypic convergence in tumours results from a consistent differential transcriptional activation of network regions of distinct evolutionary history. We coupled the time of emergence in evolution of all human genes and cellular processes with gene expression data of 7 tumour types ; and calculated the level of co-expression between cellular processes.
Tumours showed a consistent activation of network components that dated back to unicellular ancestors ; together with a widespread inactivation of multicellular processes. We also found convergent evolution of the patterns of co-expression across all tumour types ; with (1) a strong co-regulation between primitive network regions ; which are activated in concert in tumours; (2) an enhanced mutual exclusivity between network regions of a unicellular and multicellular origin. Our results provide strong ; comprehensive molecular evidence of increased reliance on primitive transcriptional programs as fundamental characteristics of tumours. Targeting regions that regulate the balance between uni- and multicellularity in tumours could provide a potential avenue for therapeutic intervention.
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