Dynamical Systems Biology of Cancer Metastasis by Mohit Kumar Jolly
International Centre for Theoretical Sciences via YouTube
Overview
Syllabus
Dynamical systems biology of cancer metastasis
uncontrolled growth of abnormal cells
Stages of cancer progression
Metastasis : the cause of 90 percent of all cancer deaths
What traits cells need to successfully metastasize?
Is genetics the answer? Not always
Can cancer proceed without mutations? Perhaps!
Can a 'systems' view help 'understand' cancer?
Example of 'systems' approach
We are...
EMT/MET: The engine of metastasis
Metastasis: a journey taken in groups
How do clusters reconcile with binary EMT?
Systems biology model for EMT/MET
Toggle switch: A systems biology model
Theoretical framework for miRNA-based circuits
Tristability in the underlying EMT network
Hybrid E/M can be a stable phenotype
Co-existence of phenotypes seen experimentally
Quantifying the EMT spectrum of states
Identifying 'phenotypic stability factors' PSFs
Knockdown of PSFs can drive a complete EMT
Spontaneous switching among phenotypes
Is EMT always reversible?
How EMT alters tumor-initiation ability stemness?
Hybrid E/M cells can form many more tumors
In vivo spontaneous EMT model highlights the aggressive behavior of hybrid E/M phenotypes
Hybrid E/M phenotype may form CTC clusters
How are CTC clusters formed?
Crosstalk between EMT and Notch pathways
Notch-Jagged signaling can form CTC clusters
JAG1 knockdown diminishes emboli formation
Why do hybrid E/M cells matter in the clinic?
Hybrid E/M: the 'fittest' for metastasis?
Conclusion
Ongoing questions/debate
Fifty or more shades of cellular plasticity
Acknowledgements
Taught by
International Centre for Theoretical Sciences