Abstract:

ABSTRACT Netrin-1 is a laminin-like protein that is secreted. It plays a role in the development of the nervous system and is also involved in processes such as cell migration, proliferation, angiogenesis, differentiation, apoptosis, metastasis, and invasion. DCC, neogenin, and UNC5 receptor families form the main receptors of netrin-1. These receptors have a dual role depending on the presence or absence of netrin-1. Netrin-1 influences carcinogenesis through signaling pathways such as PI3K/AKT, ERK/MAPK, Notch, and NF-kB. Netrin-1 receptor interactions are effective in cancer cell viability and carcinogenesis mechanisms. Overall, overexpression of netrin-1 and loss of its receptors promote carcinogenesis. Netrin-1 is involved in apoptosis through different receptors. Changes in the expression of DCC and UNC5H receptors affect cancer cell growth and metastasis. Loss of expression in dependent receptors is observed in advanced stages of various tumors. Neogenin is associated with migration and metastasis in tumors. Studies have shown that netrin-1 influences tumor development in various cancers such as gastric cancer, pancreatic ductal adenocarcinoma, colorectal cancer, and glioblastoma. Overexpression of netrin-1 is associated with poor prognosis and decreased overall survival. Netrin-1 levels are reported to be higher in patient groups compared to healthy control groups and decrease with chemotherapy. The mechanism of netrin-1 and its receptors in tumor development is not clear due to their different effects. This article summarizes research findings presenting the role and position of netrin-1 in various cancers.