Speaker
Description
Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer due to its propensity for early metastasis. MICAL (microtubule-associated monooxygenase) proteins, which are highly expressed within PDAC, directly induce actin depolymerization and indirectly cause cytoskeleton reorganization through transcription factors. Despite this knowledge, the holistic impact of MICAL2 on cytoskeleton states of cells remains unknown. Here, we have taken a multi-scale modeling approach to connect cytoskeletal gene expression programs exhibited by pancreatic cancer cells to biochemical signaling networks and extracellular matrix conditions that regulate the cellular mechanical state. Our model allows us to determine how the expression of MICAL2 impacts pancreatic cancer cell migration across soft and stiff substrates. Our preliminary results using our modeling framework indicate that MICAL2 activity confined to its direct interaction with the cytoskeletal actin network does not significantly influence cell migration. However, activation of SRF transcriptional factor downstream of MICAL2 activity towards nuclear actin significantly adds to the cytoskeletal changes and increased migration of cells in 3D environments.
