Epithelial-to-mesenchymal transition (EMT) and cell migration are pivotal processes in both cancer metastasis and embryonic development and share common molecular and genetic pathways. While EMT has long been considered essential for cancer metastasis, studies have shown that suppressing EMT by deleting key transcription factors, such as Snail or Twist, in primary tumors does not necessarily impair the invasion and metastasis of pancreatic carcinoma cells. A similar phenomenon occurs in embryonic development, where deletion of EMT-related genes leads to gastrulation defects, yet cells can ingress from the epithelial epiblast and migrate across the embryo. This paradox raises a fundamental question: What alternative molecular mechanisms enable cells to exit epithelial tissues in the absence of classical EMT factors? Here, we address this question using a novel micropatterned human pluripotent stem cell model system that captures EMT and cell migration events that occur early in embryonic development. We combine live imaging with CRISPR editing to study the interplay between genetics, EMT, and tissue morphogenesis. This strategy promises to advance our understanding of EMT and cell migration in embryogenesis, with potential implications for providing crucial insights into the mechanisms driving cancer metastasis, paving the way for new therapeutic interventions.
Figure 1. Single-cell tracking using local photoconversion. We apply patterned UV illumination to locally activate a photoconvertible green-to-red fluorescent protein (KikGR). This enables us to track single-cells undergoing EMT and migration in a dense cellular environment