Decoding the network dynamics of feedback loops among EMT and anoikis resistance in cancer metastasis

Faculty: Prof. Mohit Kumar Jolly (BE) and Prof. Annapoorni Rangarajan (DBG)

Metastasis remains a clinically unsolved challenge in cancer treatment. It is driven by phenotypic plasticity – the ability of cancer cells to reversibly alter their behaviour in response to environmental cues. Phenotypic plasticity can manifest in different forms – such as epithelial-mesenchymal transition (EMT) that enables cancer cell invasion, and anoikis-resistance that allows them to survive in bloodstream in absence of growth signals from primary tumor. Studies have shown an association between EMT and anoikis-resistance, but whether they both drive one another through feedback loops among respective molecular players remains elusive.

This project will focus on identifying how EMT and anoikis-resistance pathways regulate each other through comprehensive analysis of a) publicly available data for network inference (functional cell-based assays, high-throughput multi-omics data at bulk and/or single-cell levels), b) mechanism-based mathematical modelling investigating the emergent dynamics of underlying network, and c) experimental validation based on perturbation scenarios such as EMT induction. We will also look for clinical relevance of the impact of co-existence of these phenomenon on patient survival.

Understanding this relationship will provide insight into key metastatic mechanisms and may identify therapeutic targets to prevent colonization.

References:
https://www.nature.com/articles/cddis2013442
https://pmc.ncbi.nlm.nih.gov/articles/PMC6033311/
https://www.nature.com/articles/s41523-021-00374-x