Foxs1, a member of the forkhead box (FOX) transcriptional factor superfamily, plays crucial roles in various biological processes and diseases. It is involved in pathways such as epithelial-mesenchymal transition (EMT), angiogenesis, Hedgehog/Gli1, FAK/PI3K/AKT, and TGFβ-related pathways, influencing processes like cell proliferation, invasion, metastasis, and fibrosis [1-7]. Genetic models, such as gene knockout models, would be valuable in further elucidating its functions.

In colorectal cancer, FOXS1 promotes tumor progression by upregulating CXCL8, enhancing proliferation, invasion, and angiogenesis both in vitro and in vivo, and is associated with poor survival [1]. In prostate cancer, it promotes cancer cell growth and metastasis through the Hedgehog/Gli1 pathway, and by interacting with HILPDA to activate the FAK/PI3K/AKT pathway and initiate EMT [2,3]. In gastric cancer, FOXS1 can promote cell proliferation and EMT, while its overexpression can inhibit these processes through down-regulating the wnt/β-catenin pathway [5,9]. In liver fibrosis, FOXS1 is increased and regulates TGFβ responsiveness and proliferation pathways in human hepatic stellate cells [4]. In liver cancer, it controls EMT and predicts a poor prognosis [6]. Pan-cancer analysis shows FOXS1 is strongly expressed in various cancers, associated with low survival rates, and linked to immune-related pathways [7]. In some cases in colorectal cancer, FOXS1 acts as a tumor suppressor by promoting TGFBI degradation through the autophagy-lysosome pathway [8].

In summary, Foxs1 is a key transcriptional factor involved in multiple biological processes and disease conditions. Studies, including those potentially using KO/CKO mouse models, have revealed its significant roles in cancer progression, fibrosis, and immune-related aspects. Understanding Foxs1 can provide insights into disease mechanisms and potential therapeutic targets for cancers and liver fibrosis.

References:

1. Qiu, Junfeng, Li, Mingzhou, Su, Cailin, Liao, Wenting, Zhang, Chao. 2022. FOXS1 Promotes Tumor Progression by Upregulating CXCL8 in Colorectal Cancer. In Frontiers in oncology, 12, 894043. doi:10.3389/fonc.2022.894043. https://pubmed.ncbi.nlm.nih.gov/35898871/

2. Wang, Minyu, Huang, Wanying. 2023. FOXS1 promotes prostate cancer progression through the Hedgehog/Gli1 pathway. In Biochemical pharmacology, 218, 115893. doi:10.1016/j.bcp.2023.115893. https://pubmed.ncbi.nlm.nih.gov/37890593/

3. Ren, Ruimin, Wang, Huang, Xu, Yuan, Ma, Ding, Guan, Wei. . FOXS1 acts as an oncogene and induces EMT through FAK/PI3K/AKT pathway by upregulating HILPDA in prostate cancer. In FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 38, e23698. doi:10.1096/fj.202302654RR. https://pubmed.ncbi.nlm.nih.gov/38780613/

4. Bates, Evelyn A, Kipp, Zachary A, Lee, Wang-Hsin, Starr, Marlene E, Hinds, Terry D. 2024. FOXS1 is increased in liver fibrosis and regulates TGFβ responsiveness and proliferation pathways in human hepatic stellate cells. In The Journal of biological chemistry, 300, 105691. doi:10.1016/j.jbc.2024.105691. https://pubmed.ncbi.nlm.nih.gov/38280429/

5. Wang, Sen, Ran, Longke, Zhang, Wanfeng, Qin, Guijun, Song, Fangzhou. 2019. FOXS1 is regulated by GLI1 and miR-125a-5p and promotes cell proliferation and EMT in gastric cancer. In Scientific reports, 9, 5281. doi:10.1038/s41598-019-41717-w. https://pubmed.ncbi.nlm.nih.gov/30918291/

6. Bévant, Kevin, Desoteux, Matthis, Angenard, Gaëlle, Zucman-Rossi, Jessica, Coulouarn, Cédric. 2021. TGFβ-induced FOXS1 controls epithelial-mesenchymal transition and predicts a poor prognosis in liver cancer. In Hepatology communications, 6, 1157-1171. doi:10.1002/hep4.1866. https://pubmed.ncbi.nlm.nih.gov/34825776/

7. Liu, Yunqiang, Tu, Mengjun, Wang, Lingling. 2022. Pan-Cancer Analysis Predicts FOXS1 as a Key Target in Prognosis and Tumor Immunotherapy. In International journal of general medicine, 15, 2171-2185. doi:10.2147/IJGM.S354195. https://pubmed.ncbi.nlm.nih.gov/35241932/

8. Kuang, Yeye, Yu, Yijian, Wang, Chan, Jiang, Zhinong, Hu, Xiaotong. 2025. FOXS1, frequently inactivated by promoter methylation, inhibited colorectal cancer cell growth by promoting TGFBI degradation through autophagy-lysosome pathway. In Journal of advanced research, , . doi:10.1016/j.jare.2025.01.037. https://pubmed.ncbi.nlm.nih.gov/39864590/

9. Lu, Qiyu, Ma, Xudong, Li, Yijun, Shu, Yixiong, Wan, Baosheng. 2018. Overexpression of FOXS1 in gastric cancer cell lines inhibits proliferation, metastasis, and epithelial-mesenchymal transition of tumor through downregulating wnt/β-catenin pathway. In Journal of cellular biochemistry, 120, 2897-2907. doi:10.1002/jcb.26821. https://pubmed.ncbi.nlm.nih.gov/30500980/