Tle1-KO Mouse

Tle1, short for Transducin-like enhancer of split-1, is a transcriptional corepressor. It belongs to the Groucho/TLE/Grg family and is involved in embryogenesis, hematopoiesis, and key signaling pathways [2,3,6]. Groucho (Gro)/Transducin-like enhancer of split (TLE) family proteins act as co-repressors of many transcription factors, and Tle1 specifically has been shown to negatively regulate inflammation [1].

In cancer research, Tle1 has potential as a diagnostic marker and therapeutic target. In synovial sarcoma, it is a sensitive and specific marker with a mean sensitivity of 94% and specificity of 81% [2]. However, it is also expressed in various cutaneous neoplasms such as sebaceous neoplasms, basal cell carcinoma, and squamous cell carcinoma, indicating it is not specific to synovial sarcoma [3]. In lung cancer cells, Tle1 promotes epithelial-to-mesenchymal transition (EMT) through suppression of E-cadherin [7].

In addition, Tle1 has implications in non-cancerous conditions. For instance, in hepatic ischemia/reperfusion injury, Tle1 shelters the liver from injury by suppressing NOD2-dependent NF-κB activation [4]. In cerebral ischemia/reperfusion, Esculentoside H protects the blood-brain barrier via the TLE1/PI3K/AKT signaling pathway [5].

In conclusion, Tle1 is a crucial transcriptional corepressor involved in multiple biological processes and diseases. Its role in cancer diagnosis and as a potential therapeutic target, along with its function in ischemia/reperfusion injuries, has been revealed through various studies. These findings from different research models contribute to understanding its biological functions and offer potential directions for disease treatment.

References:

1. Yuan, Da, Yang, Xue, Yuan, Zhenpeng, Zhao, Yanqing, Guo, Junchao. . TLE1 function and therapeutic potential in cancer. In Oncotarget, 8, 15971-15976. doi:10.18632/oncotarget.13278. https://pubmed.ncbi.nlm.nih.gov/27852056/

2. El Beaino, Marc, Jupiter, Daniel C, Assi, Tarek, Araujo, Dejka M, Lin, Patrick P. 2020. Diagnostic Value of TLE1 in Synovial Sarcoma: A Systematic Review and Meta-Analysis. In Sarcoma, 2020, 7192347. doi:10.1155/2020/7192347. https://pubmed.ncbi.nlm.nih.gov/32322158/

3. Xiong, Yiqin, Dresser, Karen, Cornejo, Kristine M. . Frequent TLE1 Expression in Cutaneous Neoplasms. In The American Journal of dermatopathology, 41, 1-6. doi:10.1097/DAD.0000000000001186. https://pubmed.ncbi.nlm.nih.gov/30608261/

4. Chen, Wei, Zheng, Daofeng, Mou, Tong, Zhang, Yuke, Wu, Zhongjun. 2020. Tle1 attenuates hepatic ischemia/reperfusion injury by suppressing NOD2/NF-κB signaling. In Bioscience, biotechnology, and biochemistry, 84, 1176-1182. doi:10.1080/09168451.2020.1735928. https://pubmed.ncbi.nlm.nih.gov/32114961/

5. Zhang, Kuo, Wang, Zhi-Chao, Sun, Hongxue, Long, Huimin, Wang, Yingju. 2024. Esculentoside H reduces the PANoptosis and protects the blood-brain barrier after cerebral ischemia/reperfusion through the TLE1/PI3K/AKT signaling pathway. In Experimental neurology, 379, 114850. doi:10.1016/j.expneurol.2024.114850. https://pubmed.ncbi.nlm.nih.gov/38857750/

6. Pukhalskaya, Tatsiana, Smoller, Bruce R. 2019. TLE1 expression fails to distinguish between synovial sarcoma, atypical fibroxanthoma, and dermatofibrosarcoma protuberans. In Journal of cutaneous pathology, 47, 135-138. doi:10.1111/cup.13596. https://pubmed.ncbi.nlm.nih.gov/31614009/

7. Yao, Xin, Ireland, Shubha Kale, Pham, Tri, Raj, Madhwa H G, Biliran, Hector. 2014. TLE1 promotes EMT in A549 lung cancer cells through suppression of E-cadherin. In Biochemical and biophysical research communications, 455, 277-84. doi:10.1016/j.bbrc.2014.11.007. https://pubmed.ncbi.nlm.nih.gov/25446087/