Foxm1, also known as Forkhead box M1, is a key transcriptional regulator involved in multiple biological processes in mammals, such as carbohydrate and lipid metabolism, aging, immune regulation, development, and disease [2]. It functions by mediating transcription activation and inhibition, interacting with various co-regulators like MuvB complexes, STAT3, and β-catenin [4].

Foxm1 is often overexpressed in human solid cancers [5]. It plays a critical role in cancer cell growth, metastasis, recurrence, and stem cell features [1]. For example, in gastric cancer, RNF112-mediated ubiquitination of Foxm1 suppresses the proliferation and invasion of cancer cells, and the small-molecule compound RCM-1 enhances this process, showing anticancer effects [3]. In addition, Foxm1 impacts the outcomes of targeted therapies, chemotherapies, and immune checkpoint inhibitors in various cancer types [1]. It is also involved in non-malignant diseases, including pulmonary fibrosis, diabetes, and liver injury repair, through complex mechanisms involving multiple signaling pathways like WNT/β-catenin and STAT3/FOXM1/GLUT1 [4].

In conclusion, Foxm1 is a multifunctional transcriptional regulator. Its overexpression in cancers and involvement in non-malignant diseases make it a potential therapeutic target. The study of Foxm1, especially through models like the regulation of Foxm1 by RNF112 in gastric cancer, helps understand its role in disease development, providing insights for new treatment strategies.

References:

1. Khan, Md Arafat, Khan, Parvez, Ahmad, Aatiya, Fatima, Mahek, Nasser, Mohd Wasim. 2023. FOXM1: A small fox that makes more tracks for cancer progression and metastasis. In Seminars in cancer biology, 92, 1-15. doi:10.1016/j.semcancer.2023.03.007. https://pubmed.ncbi.nlm.nih.gov/36958703/

2. Li, Mengxi, Gao, Xuzheng, Su, Yanting, Zhang, Zhenwang, Zhu, Dan. 2024. FOXM1 transcriptional regulation. In Biology of the cell, 116, e2400012. doi:10.1111/boc.202400012. https://pubmed.ncbi.nlm.nih.gov/38963053/

3. Zhang, Shengwei, Wang, Jing, Hu, Weichao, Yang, Shiming, Hu, Changjiang. 2023. RNF112-mediated FOXM1 ubiquitination suppresses the proliferation and invasion of gastric cancer. In JCI insight, 8, . doi:10.1172/jci.insight.166698. https://pubmed.ncbi.nlm.nih.gov/37288663/

4. Zhang, Zhenwang, Li, Mengxi, Sun, Tian, Zhang, Zhengrong, Liu, Chao. 2023. FOXM1: Functional Roles of FOXM1 in Non-Malignant Diseases. In Biomolecules, 13, . doi:10.3390/biom13050857. https://pubmed.ncbi.nlm.nih.gov/37238726/

5. Borhani, Soheila, Gartel, Andrei L. 2020. FOXM1: a potential therapeutic target in human solid cancers. In Expert opinion on therapeutic targets, 24, 205-217. doi:10.1080/14728222.2020.1727888. https://pubmed.ncbi.nlm.nih.gov/32067537/