Early growth response 1 (EGR1), also known as NGF1-A, TIS8, Krox24, zif/268, and ZENK, is a transcription factor. It can be activated by various stimuli like growth factors, cytokines, apoptosis, and cellular stress states. EGR1 serves as a convergence point for signaling cascades, coupling extracellular signals to influence gene transcriptional regulation, and is involved in numerous biological processes such as tissue injury, immune responses, fibrosis, and cell proliferation [4,5].

In pancreatic cancer, EGR1 is highly expressed, promotes epithelial-mesenchymal transition (EMT) via a P300/SNAI2 pathway, and enhances cancer cell migration, invasion, and liver metastasis, suggesting blocking its expression could be a new anticancer strategy [1]. In hepatocellular carcinoma (HCC), EGR1 expression is decreased. Over-expression of EGR1 hinders HCC cell proliferation and suppresses aerobic glycolysis by down-regulating PFKL, and also increases sensitivity to sorafenib, indicating its potential as a tumor suppressor gene therapy [2]. In breast cancer, EGR1 is often downregulated, and its low expression is associated with poor survival. EGR1 overexpression inhibits cell proliferation and promotes erastin-induced ferroptosis through the Nrf2-HMOX1 signaling pathway [6,7]. In osteoporosis, EGR1 promotes osteoclastogenesis by mediating the METTL3/m6A/CHI3L1 axis [8]. In gastric cancer peritoneal metastasis, EGR1 in mesothelial cells is up-regulated, promoting epithelial-mesenchymal transformation and stemness phenotypes of gastric cancer cells through the EGR1/TGF-β1/CD44s/STAT3 signaling crosstalk [9]. Genetic inhibition of Egr1 in mouse models has been used to study its functions. For example, in AKI mouse models, genetic inhibition of Egr1 aggravates the severity of AKI, demonstrating its role in renal tubular cell regeneration as it can increase SOX9 expression in renal tubular epithelial cells [3].

In conclusion, EGR1 is a multifunctional transcription factor involved in various biological processes and diseases. Model-based research, especially using Egr1 KO/CKO mouse models, has revealed its roles in cancer (such as pancreatic, liver, breast, and gastric cancer), osteoporosis, and kidney injury. Understanding EGR1's functions provides potential therapeutic targets for these diseases.

References:

1. Wang, Yuanyang, Qin, Cheng, Zhao, Bangbo, Zhao, Yutong, Wang, Weibin. 2023. EGR1 induces EMT in pancreatic cancer via a P300/SNAI2 pathway. In Journal of translational medicine, 21, 201. doi:10.1186/s12967-023-04043-4. https://pubmed.ncbi.nlm.nih.gov/36932397/

2. Pan, Mingang, Luo, Muyu, Liu, Lele, Huang, Ailong, Xia, Jie. 2024. EGR1 suppresses HCC growth and aerobic glycolysis by transcriptionally downregulating PFKL. In Journal of experimental & clinical cancer research : CR, 43, 35. doi:10.1186/s13046-024-02957-5. https://pubmed.ncbi.nlm.nih.gov/38287371/

3. Chen, Jian-Wen, Huang, Meng-Jie, Chen, Xiao-Niao, Li, Zongjin, Chen, Xiang-Mei. 2022. Transient upregulation of EGR1 signaling enhances kidney repair by activating SOX9+ renal tubular cells. In Theranostics, 12, 5434-5450. doi:10.7150/thno.73426. https://pubmed.ncbi.nlm.nih.gov/35910788/

4. Havis, Emmanuelle, Duprez, Delphine. 2020. EGR1 Transcription Factor is a Multifaceted Regulator of Matrix Production in Tendons and Other Connective Tissues. In International journal of molecular sciences, 21, . doi:10.3390/ijms21051664. https://pubmed.ncbi.nlm.nih.gov/32121305/

5. Woodson, Caitlin M, Kehn-Hall, Kylene. 2022. Examining the role of EGR1 during viral infections. In Frontiers in microbiology, 13, 1020220. doi:10.3389/fmicb.2022.1020220. https://pubmed.ncbi.nlm.nih.gov/36338037/

6. Saha, Subbroto Kumar, Islam, S M Riazul, Saha, Tripti, Islam, Md Saiful, Cho, Ssang-Goo. . Prognostic role of EGR1 in breast cancer: a systematic review. In BMB reports, 54, 497-504. doi:. https://pubmed.ncbi.nlm.nih.gov/34488929/

7. Lin, Zhirong, Liu, Zifei, Pan, Zhilong, Gong, Chang, Chen, Jianing. 2024. EGR1 Promotes Erastin-induced Ferroptosis Through Activating Nrf2-HMOX1 Signaling Pathway in Breast Cancer Cells. In Journal of Cancer, 15, 4577-4590. doi:10.7150/jca.95328. https://pubmed.ncbi.nlm.nih.gov/39006084/

8. Wang, Changsheng, Zhang, Xiaobo, Chen, Rongsheng, Zhu, Xitian, Lian, Nancheng. 2023. EGR1 mediates METTL3/m6A/CHI3L1 to promote osteoclastogenesis in osteoporosis. In Genomics, 115, 110696. doi:10.1016/j.ygeno.2023.110696. https://pubmed.ncbi.nlm.nih.gov/37558013/

9. Jin, Yangbing, Wang, Chao, Zhang, Benyan, Yu, Beiqin, Zhang, Jun. 2024. Blocking EGR1/TGF-β1 and CD44s/STAT3 Crosstalk Inhibits Peritoneal Metastasis of Gastric Cancer. In International journal of biological sciences, 20, 1314-1331. doi:10.7150/ijbs.90598. https://pubmed.ncbi.nlm.nih.gov/38385088/