Fzd8, a G protein-coupled receptor protein belonging to the Frizzled family, is a key component in the Wnt signaling pathway. The Wnt pathway is evolutionarily conserved and involved in stem cell homeostasis, tissue regeneration, and cell fate decisions [2,5]. Fzd8, along with co-receptors LRP5 and LRP6, transduces Wnt signals, regulating numerous biological processes, and its dysregulation is associated with various diseases [5]. Genetic models, such as gene knockout mouse models, are valuable for studying Fzd8's function.

In cancer research, multiple studies have shown Fzd8's significance. In gastric cancer, Fzd8 protein expression is upregulated, promoting invasion and metastasis via the β-catenin pathway, indicating a poor prognosis [1]. In prostate cancer, high levels of Fzd8 expression are associated with clinical tumor progression and bone metastasis. Overexpressing Fzd8 promotes cell migration, invasion, and stem-cell-like phenotypes, while silencing it suppresses these processes and PCa bone metastasis in vivo [3]. In breast cancer, increased FZD8 expression is linked to clinicopathological characteristics like low survival rate, tumor vascular invasion, and molecular subtypes [4]. In papillary thyroid cancer, miR-100-5p inhibits cancer progression by targeting FZD8, inactivating the Wnt/β-catenin signaling [7]. Also, in the presence of Helicobacter pylori, overexpression of FZD8, along with other genes, enhances gastric cancer development [6].

In conclusion, Fzd8 plays a crucial role in the Wnt signaling pathway, and its dysregulation is associated with multiple cancers. Studies using gene-based models have revealed its role in promoting cancer cell invasion, metastasis, and tumorigenesis in various cancer types, highlighting its potential as a therapeutic target in cancer treatment.

References:

1. Chen, Wen, Liu, Zhiwen, Mai, Wenli, You, Xiaolong, Qin, Lei. . FZD8 Indicates a Poor Prognosis and Promotes Gastric Cancer Invasion and Metastasis via B-Catenin Signaling Pathway. In Annals of clinical and laboratory science, 50, 13-23. doi:. https://pubmed.ncbi.nlm.nih.gov/32161008/

2. Li, Na, Ge, Qiangqiang, Guo, Qiong, Tao, Yuyong. 2023. Identification and functional validation of FZD8-specific antibodies. In International journal of biological macromolecules, 254, 127846. doi:10.1016/j.ijbiomac.2023.127846. https://pubmed.ncbi.nlm.nih.gov/37926311/

3. Li, Qiji, Ye, Liping, Zhang, Xin, Song, Libing, Peng, Xinsheng. 2017. FZD8, a target of p53, promotes bone metastasis in prostate cancer by activating canonical Wnt/β-catenin signaling. In Cancer letters, 402, 166-176. doi:10.1016/j.canlet.2017.05.029. https://pubmed.ncbi.nlm.nih.gov/28602974/

4. Al-Zahrani, Maryam H, Assidi, Mourad, Pushparaj, Peter Natesan, Buhmeida, Abdelbaset, Abu-Elmagd, Muhammad. 2023. Expression pattern, prognostic value and potential microRNA silencing of FZD8 in breast cancer. In Oncology letters, 26, 477. doi:10.3892/ol.2023.14065. https://pubmed.ncbi.nlm.nih.gov/37809047/

5. Janda, Claudia Y, Dang, Luke T, You, Changjiang, Kuo, Calvin J, Garcia, K Christopher. 2017. Surrogate Wnt agonists that phenocopy canonical Wnt and β-catenin signalling. In Nature, 545, 234-237. doi:10.1038/nature22306. https://pubmed.ncbi.nlm.nih.gov/28467818/

6. Demirci, Ufuk, Orenay-Boyacioglu, Seda, Kasap, Elmas, Ellidokuz, Ender Berat, Korkmaz, Mehmet. 2023. Overexpressions of RHOA, CSNK1A1, DVL2, FZD8, and LRP5 genes enhance gastric cancer development in the presence of Helicobacter pylori. In Arab journal of gastroenterology : the official publication of the Pan-Arab Association of Gastroenterology, 24, 91-97. doi:10.1016/j.ajg.2023.01.004. https://pubmed.ncbi.nlm.nih.gov/36720664/

7. Ma, Peng, Han, Jianli. 2022. Overexpression of miR-100-5p inhibits papillary thyroid cancer progression via targeting FZD8. In Open medicine (Warsaw, Poland), 17, 1172-1182. doi:10.1515/med-2022-0490. https://pubmed.ncbi.nlm.nih.gov/35859793/