Epigenetically heterogeneous tumor cells direct collective invasion through filopodia-driven fibronectin micropatterning.

ABSTRACT: Tumor heterogeneity drives disease progression, treatment resistance, and patient relapse, yet remains largely underexplored in invasion and metastasis. Here, we investigated heterogeneity within collective cancer invasion by integrating DNA methylation and gene expression analysis in rare purified lung cancer leader and follower cells. Our results showed global DNA methylation rewiring in leader cells and revealed the filopodial motor MYO10 as a critical gene at the intersection of epigenetic heterogeneity and three-dimensional (3D) collective invasion. We further identified JAG1 signaling as a previously unknown upstream activator of MYO10 expression in leader cells. Using live-cell imaging, we found that MYO10 drives filopodial persistence necessary for micropatterning ext

SUBMITTER: Summerbell ER 

PROVIDER: S-EPMC7439406 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature