Seminar by Mohit Kumar Jolly

Physics of cellular transitions during cancer metastasis

Mohit Kumar Jolly (Centre for BioSystems Science and Engineering  Indian Institute of Science)

Metastasis – the spread of cancer cells from one organ to another – causes above 90% of all cancer-related deaths. Despite extensive ongoing efforts in cancer genomics, no unique genetic or mutational signature has emerged for metastasis. However, a hallmark that has been observed in metastasis is adaptability or phenotypic plasticity – the ability of a cell to reversibly switch among different phenotypes in response to various internal or external stimuli.

A crucial axis of phenotypic plasticity includes reversible transitions between epithelial (high cell-cell adhesion, low migration/invasion) and mesenchymal (low cell-cell adhesion, high migration/ invasion) phenotypes – EMT (Epithelial-Mesenchymal Transition) and its reverse MET. This talk will describe how mechanistic mathematical models of EMT/MET dynamics have contributed to our improved understanding of cellular decision-making at individual and population levels from these perspectives:

a) Multistability (how many cell states exist en route EMT and MET?)

b) Reversibility/irreversibility (do cells come across a ‘tipping point’ at specific time and/or dose of EMT inducers beyond which they do not revert?)

c) Hysteresis (do cells undergoing EMT/MET follow same/different paths?)

d) Cell-cell communication (how do cells affect the tendency of their neighbors to undergo EMT?)

Collectively, our work highlights how an iterative crosstalk between mathematical modeling and experiments can both generate novel insights into the emergent nonlinear dynamics of cellular transitions and uncover previously unknown accelerators of metastasis.