Tumour follower cells: A novel driver of leader cells in collective invasion (Review)

Abstract

Collective cellular invasion in malignant tumours is typically characterized by the cooperative migration of multiple cells in close proximity to each other. Follower cells are led away from the tumour by specialized leader cells, and both cell populations play a crucial role in collective invasion. Follower cells form the main body of the migration system and depend on intercellular contact for migration, whereas leader cells indicate the direction for the entire cell population. Although collective invasion can occur in epithelial and non-epithelial malignant neoplasms, such as medulloblastoma and rhabdomyosarcoma, the present review mainly provided an extensive analysis of epithelial tumours. In the present review, the cooperative mechanisms of contact inhibition locomotion between follower and leader cells, where follower cells coordinate and direct collective movement through physical (mechanical) and chemical (signalling) interactions, is summarised. In addition, the molecular mechanisms of follower cell invasion and metastasis during remodelling and degradation of the extracellular matrix and how chemotaxis and lateral inhibition mediate follower cell behaviour were analysed. It was also demonstrated that follower cells exhibit genetic and metabolic heterogeneity during invasion, unlike leader cells.

Photoactivatable substrates show diverse phenotypes of leader cells in collective migration when moving along different extracellular matrix proteins

“…Several studies have shown that the contri- bution of the follower cells to the migrating clusters goes beyond simply being dragged along passively. 2,13,30 During the migration of zebrafish polster cells, follower cells guide their migration by pulling the leader cells from behind through E-cadherin/a-catenin mechanotransduction. 31 Another work shows that followers push the leader cells during the migration of posterior lateral line primordium (PLLp) migrating within the zebrafish embryo.…”