Etv4, also known as E-twenty-six-specific sequence variant 4 or ETS variant transcription factor 4, is a transcription factor that plays crucial roles in multiple biological processes. It is involved in various signaling pathways, such as the ERK1/2, TGF-β/Smad2/3, and integrin-actomyosin pathways, and is of great biological importance in processes like lineage specification, cell proliferation, and inflammation-related tumorigenesis. Genetic models, like knockout (KO) or conditional knockout (CKO) mouse models, are valuable for studying Etv4's functions [1,2].

In hepatocellular carcinoma (HCC), Etv4 is highly expressed and its high levels predict a poor survival rate. Hepatocyte-specific knockout of Etv4 significantly prevents the development of DEN-CCL4-induced HCC, while its transgenic expression promotes HCC growth. This indicates that Etv4 promotes hepatic inflammation and HCC by activating the transcription of TNF-α and MAPK11 [2]. In bladder cancer, Etv4 enhances BCa cells-derived CXCL1/8 to recruit tumor-associated neutrophils (TANs), facilitating lymphangiogenesis and lymphatic metastasis. Depletion of neutrophils, which mimics a functional loss of Etv4's role in this context, results in a significant reduction in popliteal LN metastasis and lymphangiogenesis [3].

In conclusion, Etv4 is a key transcription factor involved in regulating various biological processes. Model-based research, especially KO/CKO mouse models, has revealed its important roles in promoting the development and metastasis of cancers such as HCC and bladder cancer. Understanding Etv4's functions provides potential therapeutic targets for these disease areas.

References:

1. Yang, Seungbok, Golkaram, Mahdi, Oh, Seyoun, Lee, Yoontae, Jang, Jiwon. 2024. ETV4 is a mechanical transducer linking cell crowding dynamics to lineage specification. In Nature cell biology, 26, 903-916. doi:10.1038/s41556-024-01415-w. https://pubmed.ncbi.nlm.nih.gov/38702503/

2. Qi, Dandan, Lu, Min, Xu, Pengfei, Liu, Ningning, Ye, Xin. 2023. Transcription factor ETV4 promotes the development of hepatocellular carcinoma by driving hepatic TNF-α signaling. In Cancer communications (London, England), 43, 1354-1372. doi:10.1002/cac2.12482. https://pubmed.ncbi.nlm.nih.gov/37670477/

3. Zhang, Qiang, Liu, Sen, Wang, Hongjin, Lin, Tianxin, Chen, Xu. 2023. ETV4 Mediated Tumor-Associated Neutrophil Infiltration Facilitates Lymphangiogenesis and Lymphatic Metastasis of Bladder Cancer. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 10, e2205613. doi:10.1002/advs.202205613. https://pubmed.ncbi.nlm.nih.gov/36670069/