Abstract
The p75 neurotrophin receptor (p75NTR), also known as low-affinity nerve growth factor, belongs to the tumor necrosis factor family of receptors. p75NTR is widely expressed in the nervous system during the development, as well as, in the neural crest population, since p75NTR has been described as ubiquitously expressed and considered as a neural crest marker. Neural crest cells (NCCs) constitute an transient population accurately migrating and invading, with precision, defined sites of the embryo. During migration, NCCs are guided along distinct migratory pathways by specialized molecules present in the extracellular matrix or on the surfaces of those cells. Two main processes direct NCC migration during the development: (1) an epithelial-to-mesenchymal transition and (2) a process known as contact inhibition of locomotion. In adults, p75NTR remains expressed by NCCs and has been identified in an increasing number of cancer cells. Nonetheless, the regulation of the expression of p75NTR and the underlying mechanisms in stem cell biology or cancer cells have not yet been sufficiently addressed. The main objective of this review is therefore to analyze elements of our actual knowledge regarding p75NTR roles during the development (mainly focusing on neural crest development) and see how we can transpose that information from development to cancer (and vice versa) to better understand the link between p75NTR and cell migration and invasion. In this review, we successively analyzed the molecular mechanisms of p75NTR when it interacts with several coreceptors and/or effectors. We then analyzed which signaling pathways are the most activated or linked to NCC migration during the development. Regarding cancer, we analyzed the described molecular pathways underlying cancer cell migration when p75NTR was correlated to cancer cell migration and invasion. From those diverse sources of information, we finally summarized potential molecular mechanisms underlying p75NTR activation in cell migration and invasion that could lead to new research areas to develop new therapeutic protocols.
Highlights
The p75 neurotrophin receptor (p75NTR) was first identified in Sutter et al (1979) and described as a low-affinity nerve growth factor (NGF) receptor
Collision between cells can cause them to move away from each other, a process known as contact inhibition of locomotion (CIL)
The link between NT, p75NTR, and ephrin in migrating Neural crest cells (NCCs) has not been described so far. It appears that during NCC invasion and migration, p75NTR may play several roles in epithelial-to-mesenchymal transition (EMT) and CIL events through several pathways including AKT, Rho-GTPase RhoA, and Jak2/signal transducer and activator of transcription 3 (STAT3). These signaling pathways seem to be mainly activated through interactions with ephrin and cadherin family members as summarized in Figures 3A, 4A, and could modulate NT effects through p75NTR and potentially coreceptors as well as through scaffold proteins
Summary
The main objective of this review is to analyze elements of our actual knowledge regarding p75NTR roles during the development (mainly focusing on neural crest development) and see how we can transpose that information from development to cancer (and vice versa) to better understand the link between p75NTR and cell migration and invasion. We analyzed the described molecular pathways underlying cancer cell migration when p75NTR was correlated to cancer cell migration and invasion. From those diverse sources of information, we summarized potential molecular mechanisms underlying p75NTR activation in cell migration and invasion that could lead to new research areas to develop new therapeutic protocols
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
