Netrin-1, a secreted laminin-related protein, was first characterized for its pivotal role in guiding axonal growth during nervous system development. However, recent research has revealed its involvement in cancer progression and metastasis. Understanding the signaling pathways through which Netrin-1 operates in cancer is crucial for elucidating its mechanisms and exploring therapeutic interventions. Netrin-1 protein controls the biological processes of cancer cells, guiding axon pathfinding and transmitting signals that are essential for migration, differentiation and cell survival via UNC5 and DCC-family receptors. To elaborate further, Netrin1 controls YAP signalling through its neogenin receptor, which affects the EMT process in gastric cancer. Researchers have also utilized the Netrin-1 protein with different nanoparticles to explore its way to prevent cancer progression. Moreover, Researchers evaluated the use of nanoparticles as an immunosensor, therapeutic and imaging tools targetting the Netrin-1 protein, which open several ways to combat cancer. This review explores how Netrin-1 influences the AKT signaling cascade impacting hippo signaling, YAP pathways and EMT process with DCC receptor. It also discusses the involvement of UNC5B and Netrin-1 in regulating ERK/MAPK signaling pathways and induction of apoptosis when Netrin-1 is absent. Moreover, it underscores the therapeutic potential of UNC5B-induced cell cycle arrest in specific cancer. Also, it delves into the diverse forms of netrin and its potential role in cancer and the glims of nanoparticles use with it. Underlining the necessity for more research to comprehend their functions in signaling cascades using the nanomaterials.
Keywords: Cancer; Metastasis suppressors; Nanoparticles; Netrin1; Oncogenic activation; UNC5B.
© 2025 The Authors. Published by Elsevier B.V.