TEAD2, a member of the TEA domain transcription factor family, is involved in crucial biological processes. It participates in the Hippo signaling pathway, which is vital for tissue growth, organ size control, and cell fate determination [1,4,5,7,9]. TEAD2 also plays a role in maintaining ground-state pluripotency in mouse embryonic stem cells, facilitating the transition between different culture conditions by mediating chromatin looping and enhancer-promoter interactions [2].

In disease-related studies, TEAD2 has been implicated in multiple cancers. In hepatocellular carcinoma (HCC), deletion of TAZ, which acts with TEAD2, consistently decreased HCC growth and mortality, while overexpression of activated TAZ triggered HCC. TAZ-and MET/CTNNB1-S45Y-driven HCC required the expression of TEAD2, and TEAD2 had a profound effect on patient survival [1]. Additionally, TEAD2 promoted HCC development and sorafenib resistance by transcriptionally activating TAK1 [4]. In pancreatic ductal adenocarcinoma, a TEAD2-driven endothelial-like program was associated with basal-like differentiation and metastasis, and genetic and pharmacologic inhibitions of TEAD2 impaired cancer progression [3]. In melanoma, vemurafenib resistance upregulated STIM1 through an EGF/EGFR-YAP1/TEAD2 signaling axis [6]. In colorectal cancer, PHF5A promoted cancer progression by alternative splicing of TEAD2 to activate YAP signaling [8].

In conclusion, TEAD2 is essential for maintaining pluripotency and plays significant roles in cancer development and progression, especially in HCC, pancreatic cancer, melanoma, and colorectal cancer. The use of gene knockout or conditional knockout mouse models in these studies has been crucial in revealing the function of TEAD2 in these biological processes and disease conditions, providing potential therapeutic targets for these cancers.

References:

1. Saito, Yoshinobu, Yin, Dingzi, Kubota, Naoto, Wangensteen, Kirk J, Schwabe, Robert F. 2023. A Therapeutically Targetable TAZ-TEAD2 Pathway Drives the Growth of Hepatocellular Carcinoma via ANLN and KIF23. In Gastroenterology, 164, 1279-1292. doi:10.1053/j.gastro.2023.02.043. https://pubmed.ncbi.nlm.nih.gov/36894036/

2. Guo, Rong, Dong, Xiaotao, Chen, Feng, Hu, Gongcheng, Yao, Hongjie. 2024. TEAD2 initiates ground-state pluripotency by mediating chromatin looping. In The EMBO journal, 43, 1965-1989. doi:10.1038/s44318-024-00086-5. https://pubmed.ncbi.nlm.nih.gov/38605224/

3. Yoo, Hye-Been, Moon, Jin Woo, Kim, Hwa-Ryeon, Kim, Mi-Young, Roe, Jae-Seok. 2023. A TEAD2-Driven Endothelial-Like Program Shapes Basal-Like Differentiation and Metastasis of Pancreatic Cancer. In Gastroenterology, 165, 133-148.e17. doi:10.1053/j.gastro.2023.02.049. https://pubmed.ncbi.nlm.nih.gov/36907523/

4. Zhang, Yahui, Ren, Yidan, Dong, Guoying, Wang, Yunshan, Zhao, Wei. . TEAD2 Promotes Hepatocellular Carcinoma Development and Sorafenib Resistance via TAK1 Transcriptional Activation. In Molecular cancer research : MCR, 22, 1102-1116. doi:10.1158/1541-7786.MCR-24-0060. https://pubmed.ncbi.nlm.nih.gov/39106149/

5. Joo, Jong Seok, Cho, Sang Yeon, Rou, Woo Sun, Eun, Hyuk Soo, Lee, Byung Seok. 2020. TEAD2 as a novel prognostic factor for hepatocellular carcinoma. In Oncology reports, 43, 1785-1796. doi:10.3892/or.2020.7578. https://pubmed.ncbi.nlm.nih.gov/32323824/

6. Bai, Weiyu, Yan, Chenghao, Yang, Yichen, Sun, Yan, Sun, Jianwei. 2024. EGF/EGFR-YAP1/TEAD2 signaling upregulates STIM1 in vemurafenib resistant melanoma cells. In The FEBS journal, 291, 4969-4983. doi:10.1111/febs.17272. https://pubmed.ncbi.nlm.nih.gov/39298503/

7. Park, Sujin, Mossmann, Dirk, Chen, Qian, Heim, Markus H, Hall, Michael N. . Transcription factors TEAD2 and E2A globally repress acetyl-CoA synthesis to promote tumorigenesis. In Molecular cell, 82, 4246-4261.e11. doi:10.1016/j.molcel.2022.10.027. https://pubmed.ncbi.nlm.nih.gov/36400009/

8. Chang, Yue, Zhao, Yulu, Wang, Liya, Chu, Xiaoyuan, Chen, Cheng. 2021. PHF5A promotes colorectal cancerprogression by alternative splicing of TEAD2. In Molecular therapy. Nucleic acids, 26, 1215-1227. doi:10.1016/j.omtn.2021.10.025. https://pubmed.ncbi.nlm.nih.gov/34853721/

9. Alder, Olivia, Cullum, Rebecca, Lee, Sam, Marra, Marco A, Hoodless, Pamela A. 2014. Hippo signaling influences HNF4A and FOXA2 enhancer switching during hepatocyte differentiation. In Cell reports, 9, 261-271. doi:10.1016/j.celrep.2014.08.046. https://pubmed.ncbi.nlm.nih.gov/25263553/