Fzd7, short for Frizzled class receptor 7, is a key Wnt signaling receptor. It can transduce both canonical and noncanonical Wnt signals, which are crucial for various biological processes such as cell proliferation, differentiation, and development [10]. The Wnt signaling pathway, in which Fzd7 is involved, plays a significant role in embryonic development, tissue homeostasis, and disease, especially cancer. Genetic models, like KO/CKO mouse models, are valuable for studying Fzd7's functions.

In multiple cancers, Fzd7 shows abnormal expression and is associated with tumor progression. In intrahepatic cholangiocarcinoma, circACTN4 recruits YBX1 to initiate FZD7 transcription, promoting tumor proliferation and metastasis [1]. In melanoma, WNT11-FZD7-DAAM1 signaling regulates tumour-initiating potential, local invasion, and distant metastasis [2]. For endometriosis, FZD7 expression is higher compared to normal endometrium and may promote its progression [3]. In pancreatic cancer, Fzd7/Wnt7b signaling contributes to stemness and chemoresistance, and FZD7 accelerates hepatic metastases by promoting EMT and strengthening cell stemness [4,6]. In ovarian cancer, FZD7 is highly expressed in certain subtypes, and a specific antibody-drug conjugate can induce tumor regression; also, FZD7+ platinum-tolerant cells are susceptible to ferroptosis, and the FZD7-TWIST1 axis is responsible for anoikis resistance and tumorigenesis [5,9,10]. Additionally, in immature porcine Sertoli cells, FZD7, regulated by non-CpG methylation, is important for cell proliferation [8]. A FZD7 polypeptide vaccine can activate the immune response and play a role in tumor suppression in TNBC [7].

In conclusion, Fzd7 is a vital Wnt signaling receptor with diverse functions in development and disease. Model-based research, especially through KO/CKO mouse models (although not explicitly detailed in all references), has revealed its significant roles in cancer progression, endometriosis, and Sertoli cell proliferation. Understanding Fzd7's functions provides potential targets for therapeutic intervention in related diseases.

References:

1. Chen, Qinjunjie, Wang, Haibo, Li, Zheng, Wang, Kui, Shen, Feng. 2021. Circular RNA ACTN4 promotes intrahepatic cholangiocarcinoma progression by recruiting YBX1 to initiate FZD7 transcription. In Journal of hepatology, 76, 135-147. doi:10.1016/j.jhep.2021.08.027. https://pubmed.ncbi.nlm.nih.gov/34509526/

2. Rodriguez-Hernandez, Irene, Maiques, Oscar, Kohlhammer, Leonie, Malanchi, Ilaria, Sanz-Moreno, Victoria. 2020. WNT11-FZD7-DAAM1 signalling supports tumour initiating abilities and melanoma amoeboid invasion. In Nature communications, 11, 5315. doi:10.1038/s41467-020-18951-2. https://pubmed.ncbi.nlm.nih.gov/33082334/

3. Lan, Suwei, Zhang, Zhengmao, Li, Qing. . FZD7: A potential biomarker for endometriosis. In Medicine, 102, e35406. doi:10.1097/MD.0000000000035406. https://pubmed.ncbi.nlm.nih.gov/37800830/

4. Zhang, Zhongbo, Xu, Yuanhong, Zhao, Chenghai. 2021. Fzd7/Wnt7b signaling contributes to stemness and chemoresistance in pancreatic cancer. In Cancer medicine, 10, 3332-3345. doi:10.1002/cam4.3819. https://pubmed.ncbi.nlm.nih.gov/33934523/

5. Do, Myan, Wu, Christina C N, Sonavane, Pooja R, Advani, Sunil J, Willert, Karl. 2021. A FZD7-specific Antibody-Drug Conjugate Induces Ovarian Tumor Regression in Preclinical Models. In Molecular cancer therapeutics, 21, 113-124. doi:10.1158/1535-7163.MCT-21-0548. https://pubmed.ncbi.nlm.nih.gov/34667113/

6. Zhang, Zhongbo, Xu, Yuanhong. 2022. FZD7 accelerates hepatic metastases in pancreatic cancer by strengthening EMT and stemness associated with TGF-β/SMAD3 signaling. In Molecular medicine (Cambridge, Mass.), 28, 82. doi:10.1186/s10020-022-00509-1. https://pubmed.ncbi.nlm.nih.gov/35854234/

7. Hua, Zhongke, Han, Yu, Liu, Kan, Wu, Christina C N, Wang, Xiaomei. 2022. Antitumor effect and mechanism of FZD7 polypeptide vaccine. In Frontiers in oncology, 12, 925495. doi:10.3389/fonc.2022.925495. https://pubmed.ncbi.nlm.nih.gov/36276155/

8. Yang, Anqi, Yan, Saina, Yin, Yanfei, Ran, Maoliang, Chen, Bin. 2023. FZD7, Regulated by Non-CpG Methylation, Plays an Important Role in Immature Porcine Sertoli Cell Proliferation. In International journal of molecular sciences, 24, . doi:10.3390/ijms24076179. https://pubmed.ncbi.nlm.nih.gov/37047150/

9. Wang, Yinu, Zhao, Guangyuan, Condello, Salvatore, Cheng, Ji-Xin, Matei, Daniela. 2020. Frizzled-7 Identifies Platinum-Tolerant Ovarian Cancer Cells Susceptible to Ferroptosis. In Cancer research, 81, 384-399. doi:10.1158/0008-5472.CAN-20-1488. https://pubmed.ncbi.nlm.nih.gov/33172933/

10. Tan, Ming, Asad, Mohammad, Heong, Valerie, Scott, Clare, Huang, Ruby Yun-Ju. 2019. The FZD7-TWIST1 axis is responsible for anoikis resistance and tumorigenesis in ovarian carcinoma. In Molecular oncology, 13, 757-780. doi:10.1002/1878-0261.12425. https://pubmed.ncbi.nlm.nih.gov/30548372/