Fzd9, also known as Frizzled 9 and CD349, is a transmembrane receptor of the frizzled family that functions as a Wnt signaling receptor. It plays a crucial role in various biological processes, including fetal neurologic and bone development, and is involved in maintaining normal epithelial phenotypes in the lung [3,4,5].

In a Myc-driven insulinoma mouse model, the lack of Fzd9 impaired sustained tumor expansion and β-cell dedifferentiation, indicating its essentiality for Myc-induced tumorigenesis in pancreatic islets [1]. In the urethane lung adenocarcinoma model using Fzd9-/-mice, Fzd9 deficiency led to more proliferation, increased EMT signaling, and other malignant-like changes in adenomas, suggesting its role in preventing premalignant lung lesion development [3]. In triple-negative breast cancer, in silico analysis showed that Fzd9 was differentially expressed and high levels were associated with poor survival, though in-vitro and in-vivo validation is needed [2].

In summary, Fzd9 is essential for maintaining normal cell phenotypes and physiological structures in various tissues. Its deficiency in KO mouse models reveals its role in tumorigenesis in pancreatic islets and lung, highlighting its potential as a target for cancer intervention. The in-silico analysis in triple-negative breast cancer also suggests its potential as a prognostic biomarker [1,2,3].

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. 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/

4. Shi, Qiusheng, Gui, Jinpeng, Sun, Lianwen, Fan, Yubo, Zheng, Lisha. . Frizzled-9 triggers actin polymerization and activates mechano-transducer YAP to rescue simulated microgravity-induced osteoblast dysfunction. In FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 37, e23147. doi:10.1096/fj.202300977R. https://pubmed.ncbi.nlm.nih.gov/37585277/

5. 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/