Abstract

Cancer cells invade collectively with leader-follower organization. However, how leader cells are regulated during the dynamic invasion process remains poorly understood. Using a FRET nanobiosensor that tracks lncRNA dynamics in live single cells, we monitored the spatiotemporal distribution of lncRNA during collective cancer invasion. We show that lncRNA MALAT1 is dynamically regulated in the invading fronts of cancer cells and patient-derived organoids. The abundance, diffusivity, and distribution of MALAT1 transcripts are distinct between leader and follower cells. MALAT1 expression increases when a cell acquires the leader cell role and decreases when the migration process stops. Transient knockdown of MALAT1 prevents the formation of leader cells and abolishes the migration of cancer cells. Taken together, our single cell analysis suggests MALAT1 dynamically regulates leader cells during collective cancer invasion.