The ARF GTPase regulatory network in collective invasion and metastasis

Abstract

The ability to remodel and move cellular membranes, and the cargoes regulated by these membranes, allows for specialised functions to occur in distinct regions of the cell in a process known as cellular polarisation. The ability to collectively co-ordinate such polarisation between cells allows for the genesis of multicellularity, such as the formation of organs. During tumourigenesis, the rules for such tissue polarisation become dysregulated, allowing for collective polarity rearrangements that can drive metastasis. In this review, we focus on how membrane trafficking underpins collective cell invasion and metastasis in cancer. We examine this through the lens of the ADP-ribosylation factor (ARF) subfamily of small GTPases, focusing on how the ARF regulatory network — ARF activators, inactivators, effectors, and modifications — controls ARF GTPase function.

The calcium pump PMCA4b promotes epithelial cell polarization and lumen formation

“…The ADP-ribosylation factor 6 (Arf6) small GTPase protein regulates membrane trafficking pathways (Li et al, 2017), and it has also been implicated in cell polarization (Ikenouchi & Umeda, 2010;Osmani et al, 2010;Shteyn et al, 2011) and lumenogenesis (Clancy et al, 2018;Tushir et al, 2010). Although Arf6 is essential for cell polarization, Arf6 hyperactivity can promote invasiveness and metastatic activity of cancer cells (Li et al, 2017;Nikolatou et al, 2023) by increasing their motility (Zobel et al, 2018).…”