Ntrk3-KO Mouse

Ntrk3, also known as the neurotrophin-3 receptor, is a protein-tyrosine kinase that plays crucial roles in multiple biological processes. It is involved in signaling cascades such as the Ras-MAP kinase and PI3K-AKT pathways through the IRS-1 adapter protein [6]. Ntrk3 is important in the development and organization of certain cell populations, like gonadotrope cells where it regulates cell adhesion, motility, and positioning within the pituitary gland via the Neurod1/4-Ntrk3-cSrc pathway [10].

Ntrk3 gene fusions have been identified in various cancers, acting as oncogenic drivers. In breast and salivary gland secretory carcinomas, the ETV6-NTRK3 fusion is characteristic, leading to constitutive activation of tropomyosin receptor kinase C protein, promoting cell survival, growth, and proliferation [4,7]. In other cancers such as infantile fibrosarcoma, melanoma, glioma, and carcinomas of the thyroid, lung, colon, prostate, and gastrointestinal stromal tumors (GISTs), Ntrk3 fusions are less common but still significant [1,2,3,5,9]. In upper tract urothelial carcinomas (UTUC), higher Ntrk3 expression is correlated with worse survival outcomes, and it may promote cancer by interacting with the PI3K-AKT-mTOR signaling pathway [8].

In conclusion, Ntrk3 is essential for normal cell functions like cell adhesion and motility in specific cell types. Its gene fusions are key oncogenic drivers in multiple cancers, highlighting its importance in cancer research. Understanding Ntrk3 through functional studies, including those using gene knockout models in vivo, provides insights into disease mechanisms and potential therapeutic targets for treating cancers driven by Ntrk3 fusions [1-10].