On the move: endocytic trafficking in cell migration

Abstract

Directed cell migration is a fundamental process underlying diverse physiological and pathophysiological phenomena ranging from wound healing and induction of immune responses to cancer metastasis. Recent advances reveal that endocytic trafficking contributes to cell migration in multiple ways. (1) At the level of chemokines and chemokine receptors: internalization of chemokines by scavenger receptors is essential for shaping chemotactic gradients in tissue, whereas endocytosis of chemokine receptors and their subsequent recycling is key for maintaining a high responsiveness of migrating cells. (2) At the level of integrin trafficking and focal adhesion dynamics: endosomal pathways do not only modulate adhesion by delivering integrins to their site of action, but also by supplying factors for focal adhesion disassembly. (3) At the level of extracellular matrix reorganization: endosomal transport contributes to tumor cell migration not only by targeting integrins to invadosomes but also by delivering membrane type 1 matrix metalloprotease to the leading edge facilitating proteolysis-dependent chemotaxis. Consequently, numerous endocytic and endosomal factors have been shown to modulate cell migration. In fact key modulators of endocytic trafficking turn out to be also key regulators of cell migration. This review will highlight the recent progress in unraveling the contribution of cellular trafficking pathways to cell migration.

miRNA-223 inhibits epithelial-mesenchymal transition in gastric carcinoma cells via Sp1

“…This process depends on the interaction between cancer cells and the local tumor environment which promotes their survival, growth, invasion, and ultimately metastasis (26). EMT, which drives many of these processes, is therefore a major factor contributing to the invasion and metastasis of cancer cells (27)(28)(29).…”

A new front in cell invasion: The invadopodial membrane

“…Examples of directed membrane trafficking include include neurite outgrowth (Hausott and Klimaschewski, 2016), neuronal and immunological synapse function (Gonnord et al, 2012), wound healing (Abreu-Blanco et al, 2011), cell division (Shuster and Burgess, 2002), and cell migration (Maritzen et al, 2015). Targeted vesicle delivery requires a source of internal vesicles/membrane, exocytic trafficking machinery, and when vesicles are dynamically recycled, endocytic recycling components (Grant and Donaldson, 2009).…”

Chemokines in tumor proximal fluids

“…It is widely accepted that these molecules are secreted into the extracellular space and retained there by binding to extracellular matrix glycosaminoglycans, thereby establishing immobilized gradients 2 . A chemotactic gradient can also be built by modifying the activity of chemokines through MMP9-mediated cleavage, or it can be shaped by removing the chemoattractant by scavenger receptors 3 . Due to the optical clarity of the zebrafish embryos, the migration of neutrophils and primordial germ cells can be imaged at a high resolution based on the dynamic expression of the homologs of the human CXCL8 and CXCL12, respectively, and their receptors 4 .…”

“…This signaling can in turn modulate cytoskeletal protein configuration and integrin affinity. Cell migration is a spatially organized process that begins with the polarization of the cell, developing a distinguish- able leading edge and trailing end, followed by changes in cell adhesion 3 . Since Wirchow's seminal observation that leukocytes are present in tumor tissues, empirical evidence has underscored inflammation as both a cause and a consequence of cancer.…”