Aymelek GÖNENÇ, Hülya KARA

Netrin-1 ve Reseptörlerinin Çeşitli Kanserlerdeki Rolü

ÖZ Netrin-1 laminin benzeri, salgılanan bir proteindir. Sinir sistemi gelişiminde rolü olan netrin-1, hücre göçü, proliferasyon, anjiyogenez, farklılaşma, apopitoz, metastaz, invazyon gibi süreçlerde de yer almaktadır. DCC, neogenin ve UNC5 reseptör ailesi netrin-1’ in ana reseptörlerini oluşturmaktadır. Bu reseptörler netrin-1’in varlığına veya yokluğuna bağlı olarak ikili bir rol oynamaktadır. Netrin-1 karsinogenezde PI3K/AKT, ERK/MAPK, Notch, NF-kB gibi sinyal yolaklarını kullanarak etki etmektedir. Kanser hücresinin canlılığında ve karsinogenez mekanizmasında netrin-1 reseptör etkileşimleri etkili olmaktadır. Genel olarak netrin-1’in aşırı ifadesi ve reseptörlerinin kaybı karsinogenezi teşvik etmektedir. Netrin-1 apopitozda farklı reseptörler aracılığıyla görev almaktadır. DCC ve UNC5H reseptörlerin ifadesinin değişmesi kanser hücre büyümesini ve metastazını etkilemektedir. Çeşitli tümörlerde ileri evrede bağımlı reseptörlerde ekspresyon kaybı gözlenmektedir. Tümörlerde neogenin migrasyon ve metastaz ile ilişkilendirilmektedir. Yapılan araştırmalar netrin-1 ‘in mide kanseri, pankreas duktal adenokarsinomu, kolorektal kanser, glioblastom gibi çeşitli kanserlerde tümör gelişiminde etki gösterdiğini kanıtlamaktadır. Netrin-1’in aşırı ekspresyonu hastalığın kötü prognozu ile ilişkilendirilmektedir ve genel sağ kalım azalmaktadır. Netrin-1 düzeylerinin sağlıklı kontrol grubuna göre hasta grubunda daha yüksek olduğu ve kemoterapi ile ekspresyonun azaldığı bildirilmektedir. Netrin-1 ve reseptörlerinin tümör gelişimindeki mekanizması farklı etkilerinden dolayı net değildir. Bu makalede netrin-1’in çeşitli kanserlerde yerini ve rolünü sunan araştırma bulguları özetlenmiştir.

Anahtar Kelimeler:

Netrin-1, DCC, UNC5, kanser, apopitoz

The Role of Netrin-1 and Its Receptors in Various Cancers

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.

Keywords:

Netrin-1, DCC, UNC5, cancer, apoptosis,

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