Fzd1, a Frizzled class receptor, is a key component of the Wnt signaling pathway. The Wnt pathway is crucial in controlling stem cell specification and activity in numerous species [1,2]. Fzd1 has been implicated in various biological processes and diseases, highlighting its overall biological importance. Genetic models, such as knockout (KO) mouse models, have been instrumental in studying its functions.

In mice, the creation of Fzd1 -null mice revealed that while most Fzd1(-/-) females were subfertile, rare ones were sterile due to uterine fibrosis and ovarian tubulostromal hyperplasia. Gene expression analyses of cumulus-oocyte complexes from these mice showed a blunted response of oocyte and cumulus genes to the ovulatory signal, indicating Fzd1 is required for normal female fertility and may regulate oocyte maturation and cumulus cell function [5]. In addition, in multidrug-resistant MES-SA/Dx5 cancer cells, inhibition of Fzd1 using curcumin or FZD1 shRNA knockdown reduced cell viability and drug pump-out ability, suggesting Fzd1 regulates PKCδ, and the PKCδ/AP-1 signalling transduction pathway plays a role in drug resistance [4].

In conclusion, Fzd1 plays essential roles in normal female fertility and drug resistance in certain cancer cells as revealed through model-based research. The Fzd1 KO mouse models have contributed significantly to understanding its functions in female reproduction-related diseases and cancer drug resistance. Additionally, Fzd1 may also be involved in other biological processes and diseases such as glioblastoma, clear cell renal cell carcinoma, pancreatic ductal adenocarcinoma, and lung adenocarcinoma, based on studies showing its potential as a biomarker or therapeutic target in these conditions [3,6,7,8].

References:

1. Nabhan, Ahmad N, Webster, Joshua D, Adams, Jarret J, Arron, Joseph R, Dixit, Vishva M. 2023. Targeted alveolar regeneration with Frizzled-specific agonists. In Cell, 186, 2995-3012.e15. doi:10.1016/j.cell.2023.05.022. https://pubmed.ncbi.nlm.nih.gov/37321220/

2. Park, Hyun Woo, Kim, Young Chul, Yu, Bo, Wang, Cun-Yu, Guan, Kun-Liang. . Alternative Wnt Signaling Activates YAP/TAZ. In Cell, 162, 780-94. doi:10.1016/j.cell.2015.07.013. https://pubmed.ncbi.nlm.nih.gov/26276632/

3. Jia, Fang, Zhang, Lixia, Jiang, Zhengye, Tan, Guowei, Wang, Zhanxiang. 2023. FZD1/KLF10-hsa-miR-4762-5p/miR-224-3p-circular RNAs axis as prognostic biomarkers and therapeutic targets for glioblastoma: a comprehensive report. In BMC medical genomics, 16, 21. doi:10.1186/s12920-023-01450-w. https://pubmed.ncbi.nlm.nih.gov/36755291/

4. Hung, Tsai-Hsien, Chen, Chuan-Mu, Tseng, Ching-Ping, Choo, Kong-Bung, Chong, Kowit Yu. 2014. FZD1 activates protein kinase C delta-mediated drug-resistance in multidrug-resistant MES-SA/Dx5 cancer cells. In The international journal of biochemistry & cell biology, 53, 55-65. doi:10.1016/j.biocel.2014.04.011. https://pubmed.ncbi.nlm.nih.gov/24814288/

5. Lapointe, Evelyne, Boyer, Alexandre, Rico, Charlène, Richards, JoAnne S, Boerboom, Derek. 2012. FZD1 regulates cumulus expansion genes and is required for normal female fertility in mice. In Biology of reproduction, 87, 104. doi:10.1095/biolreprod.112.102608. https://pubmed.ncbi.nlm.nih.gov/22954793/

6. Peng, Qiang, Wang, Lu, Zhao, Danfeng, Wang, Jiaqi, Xu, Wanhai. 2019. Overexpression of FZD1 is Associated with a Good Prognosis and Resistance of Sunitinib in Clear Cell Renal Cell Carcinoma. In Journal of Cancer, 10, 1237-1251. doi:10.7150/jca.28662. https://pubmed.ncbi.nlm.nih.gov/30854133/

7. Yang, Liangliang, Yang, Zhulin, Li, Daiqiang, Yuan, Yuan, Xu, Huilan. 2017. Overexpression of FZD1 and CAIX are Associated with Invasion, Metastasis, and Poor-Prognosis of the Pancreatic Ductal Adenocarcinoma. In Pathology oncology research : POR, 24, 899-906. doi:10.1007/s12253-017-0284-5. https://pubmed.ncbi.nlm.nih.gov/28921449/

8. Wang, Ronghua, Wang, Xiuyun, Zhang, Jingtao, Liu, Yanpei. . LINC00942 Promotes Tumor Proliferation and Metastasis in Lung Adenocarcinoma via FZD1 Upregulation. In Technology in cancer research & treatment, 20, 1533033820977526. doi:10.1177/1533033820977526. https://pubmed.ncbi.nlm.nih.gov/34253104/