Our lab investigates how cancer cells acquire the ability to invade their surroundings. It is a key early step in the lethal progression to metastasis. The majority of human cancers occurs in epithelial tissue in which proliferation and migration of normal epithelial cells are ordinarily held in check. When growth inhibition is broken or disrupted, cells proliferate chaotically, forming a primary tumor mass. At this stage, the disease is benign. The lethal phase begins when cancer cells gain the capacity to migrate and invade into the surrounding matrix. Invasion enables cancer cells to reach and infiltrate nearby blood vessels through which they travel and colonize secondary sites.
We study how changes in molecular pathways within cancer cells1 and alterations outside the cell in the surrounding microenvironment2 work together to transform normal cells into invasive cancer cells. We seek to identify robust therapeutic strategies to target cancer cells whose heterogeneity and plasticity make them a “moving target”. Because the properties of cancer cells are non-uniform and closely coupled to their microenvironmental context, we image and analyze single-cell behaviors in microscale environments. We engineer these environments to mimic, isolate and tune critical features in order to better understand the relationship between properties of the microenvironment and cancer cell invasiveness.
EGFR and TGF\(\beta\) signaling, MAP kinase, E-cadherin, apical-basal regulator PARD3, Notch. ↩︎
matrix density and stiffening, spatial constraints ↩︎