Abstract
Cell motility is a central process involved in fundamental biological phenomena during embryonic development, wound healing, immune surveillance, and cancer spreading. Cell movement is complex and dynamic and requires the coordinated activity of cytoskeletal, membrane, adhesion and extracellular proteins. Cellular prion protein (PrPC) has been implicated in distinct aspects of cell motility, including axonal growth, transendothelial migration, epithelial–mesenchymal transition, formation of lamellipodia, and tumor migration and invasion. The preferential location of PrPC on cell membrane favors its function as a pivotal molecule in cell motile phenotype, being able to serve as a scaffold protein for extracellular matrix proteins, cell surface receptors, and cytoskeletal multiprotein complexes to modulate their activities in cellular movement. Evidence points to PrPC mediating interactions of multiple key elements of cell motility at the intra- and extracellular levels, such as integrins and matrix proteins, also regulating cell adhesion molecule stability and cell adhesion cytoskeleton dynamics. Understanding the molecular mechanisms that govern cell motility is critical for tissue homeostasis, since uncontrolled cell movement results in pathological conditions such as developmental diseases and tumor dissemination. In this review, we discuss the relevant contribution of PrPC in several aspects of cell motility, unveiling new insights into both PrPC function and mechanism in a multifaceted manner either in physiological or pathological contexts.
Highlights
Cell motility is a fundamental process that entails intracellular remodeling, an intricate molecular network, and several cell–milieu interactions [1]
Those microfilaments play a major role in the generation of cell polarity, since they are responsible for the formation of dynamic membrane protrusions of the cell edge, such as lamellipodia, filopodia, cell cortex, microvilli, as well as stress fibers that generate focal adhesions (FA) to the substratum, and in cytokinesis for cell division [9]
The spatial localization of PrPC in microdomains of the plasma membrane might dictate the distribution of Src family signaling partners and consequent activation of different cellular events. Another way PrPC appears involved with cell–cell adhesion is through interactions with desmosomal proteins, and this has been demonstrated both in enterocytes and brain microvascular endothelial cells (BMVEC) [70,71]
Summary
Cell motility is a fundamental process that entails intracellular remodeling, an intricate molecular network, and several cell–milieu interactions [1]. Actin represents one of the main proteins in the cytoskeleton and its polymerization is key in the assembly and dynamic behavior of microfilaments [8] Those microfilaments play a major role in the generation of cell polarity, since they are responsible for the formation of dynamic membrane protrusions of the cell edge, such as lamellipodia, filopodia, cell cortex, microvilli, as well as stress fibers that generate focal adhesions (FA) to the substratum, and in cytokinesis for cell division [9]. This review discusses the biological processes involved in cell motility and migration, highlighting the participation of PrPC as a signaling organizer in these mechanisms for the proper functioning of cells under physiological conditions, as well as in the progression of cancer, focusing on PrPC as a player in invasion and metastasis events of several types of neoplasm
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