Bioinformatics Seminar
Time: 11AM
Venue: Zoom Webinar
7 December 2021
The role of plasticity in tumour heterogeneity and cancer progression
Holly WhitfieldWEHI Bioinformatics
Metastatic organotropism and adaptation to metastatic environments are mediated by plastic response to microenvironment cues. However, many open questions remain regarding the mechanisms that enable subpopulations of cells to compete, disseminate, and establish secondary tumours. To investigate these questions, a Lentiviral Gene Ontology (LeGO) vector-barcoded breast cancer cell-line was developed as a model for tumour progression. Our LeGO-barcoded model allows high-quality in situ imaging of organs before sequencing and has been optimised to provide exponentially more fluorescent colour combinations than previous studies. As a xenograft into mice our model reliably produces site-specific metastases. This has enabled us to study the spatiotemporal evolution of metastatic breast cancer subclones throughout tumour progression.
Using our xenograft model, I derived a niche-specific transcriptomic signal that captures breast cancer organotropism. We found that this gene expression pattern was reversible and reflects plastic adaptability to metastatic environments, revealing a potential mechanism for lung organotropism. I will also present some preliminary work investigating an aggressive subclone with a distinct transcriptomic signature