Fzd9, a member of the frizzled gene family, codes for a putative Wnt receptor. It has a cysteine-rich extracellular domain and seven transmembrane domains. Fzd9 is involved in multiple biological processes such as embryonic development, tissue architecture regulation, and organogenesis through Wnt signaling pathways [3]. Genetic models, especially mouse models, have been crucial for studying its functions.

In a Myc-driven insulinoma mouse model, the lack of Fzd9 impairs sustained tumor expansion and β-cell dedifferentiation, maintaining pancreatic islets' physiological structure and affecting Myc-related global gene expression, indicating its essential role in Myc-induced tumorigenesis in pancreatic islets [1]. In triple-negative breast cancer (TNBC), in silico analysis showed Fzd9 was among the top differentially expressed genes, with high levels associated with worse survival, suggesting it may be a potential prognostic biomarker [2]. In lung cells, knockdown of Fzd9 in human bronchial epithelial cell lines altered downstream EMT targets and PPARγ activity, and Fzd9-/-mice in a lung adenocarcinoma model had more tumor-related phenotypes, indicating its role in lung epithelial maintenance and smoking-related malignant transformation [4].

In conclusion, Fzd9 plays essential roles in multiple biological processes and disease conditions. Mouse models, especially gene-knockout models, have been instrumental in revealing its function in tumorigenesis, such as in pancreatic islets and the lung, as well as its potential as a biomarker in TNBC. These studies contribute to understanding disease mechanisms and developing potential therapeutic strategies.

References:

1. Zacarías-Fluck, Mariano F, Jauset, Toni, Martínez-Martín, Sandra, Evan, Gerard I, Soucek, Laura. 2021. The Wnt signaling receptor Fzd9 is essential for Myc-driven tumorigenesis in pancreatic islets. In Life science alliance, 4, . doi:10.26508/lsa.201900490. https://pubmed.ncbi.nlm.nih.gov/33653688/

2. de Bastos, Daniel Rodrigues, Conceição, Mércia Patrícia Ferreira, Michelli, Ana Paula Picaro, Vilanova-Costa, Cesar Augusto Sam Tiago, Silva, Antonio Márcio Teodoro Cordeiro. 2020. An In Silico Analysis Identified FZD9 as a Potential Prognostic Biomarker in Triple-Negative Breast Cancer Patients. In European journal of breast health, 17, 42-52. doi:10.4274/ejbh.2020.5804. https://pubmed.ncbi.nlm.nih.gov/33796830/

3. Wang, Y K, Spörle, R, Paperna, T, Schughart, K, Francke, U. . Characterization and expression pattern of the frizzled gene Fzd9, the mouse homolog of FZD9 which is deleted in Williams-Beuren syndrome. In Genomics, 57, 235-48. doi:. https://pubmed.ncbi.nlm.nih.gov/10198163/

4. Sompel, Kayla, Dwyer-Nield, Lori D, Smith, Alex J, Keith, Robert L, Tennis, Meredith A. 2022. Loss of Frizzled 9 in Lung Cells Alters Epithelial Phenotype and Promotes Premalignant Lesion Development. In Frontiers in oncology, 12, 815737. doi:10.3389/fonc.2022.815737. https://pubmed.ncbi.nlm.nih.gov/35924166/