Tfcp2l1, also known as CRTR-1 and LBP-9, is a transcription factor belonging to the TFCP2/Grainyhead family. It is crucial for maintaining the pluripotency and self-renewal of embryonic stem cells. Tfcp2l1 may be involved in multiple pathways, such as the Wnt/β-catenin signaling pathway, as inhibition of this pathway can eliminate the differentiation caused by Tfcp2l1 down-regulation [4]. It plays a significant role in various biological processes and disease conditions, making genetic models valuable for its study.

In renal medullary carcinoma, the loss of renal epithelial transcription factor Tfcp2l1 is associated with the transformation of thick ascending limb cells into an epithelial-mesenchymal gradient of RMC cells, along with the gain of MYC and NFE2L2-associated oncogenic and ferroptosis resistance programs [1]. In hepatocellular carcinoma, knockdown of Tfcp2l1 significantly reduces HCC cell proliferation, invasion, and other malignant behaviors, while overexpression enhances them. It promotes the stemness of cancer stem cells by upregulating NANOG and activating the JAK/STAT3 pathway [2]. In thyroid cancer, Tfcp2l1 is significantly downregulated, and its decreased expression is related to malignant clinicopathological characteristics. Overexpression of Tfcp2l1 in thyroid cancer cells inhibits cell growth and motility in vitro and tumorigenicity and metastasis in vivo, likely by inactivating the NF-κB signaling pathway [3].

In conclusion, Tfcp2l1 is essential for maintaining the pluripotency of embryonic stem cells. Model-based research, especially gene knockout studies, has revealed its role in various cancers, including renal medullary carcinoma, hepatocellular carcinoma, and thyroid cancer. Understanding Tfcp2l1 can provide insights into the mechanisms of cancer development and potential therapeutic targets.

References:

1. Vokshi, Bujamin H, Davidson, Guillaume, Tawanaie Pour Sedehi, Nassim, Davidson, Irwin, Malouf, Gabriel G. 2023. SMARCB1 regulates a TFCP2L1-MYC transcriptional switch promoting renal medullary carcinoma transformation and ferroptosis resistance. In Nature communications, 14, 3034. doi:10.1038/s41467-023-38472-y. https://pubmed.ncbi.nlm.nih.gov/37236926/

2. Qiu, Dongbo, Wang, Tiantian, Xiong, Yi, Zhang, Qi, Jia, Changchang. 2024. TFCP2L1 drives stemness and enhances their resistance to Sorafenib treatment by modulating the NANOG/STAT3 pathway in hepatocellular carcinoma. In Oncogenesis, 13, 33. doi:10.1038/s41389-024-00534-1. https://pubmed.ncbi.nlm.nih.gov/39266516/

3. Zeng, C, Zhang, Y, Lin, C, Li, Y, Guan, H. 2024. TFCP2L1, a potential differentiation regulator, predicts favorable prognosis and dampens thyroid cancer progression. In Journal of endocrinological investigation, 47, 2953-2968. doi:10.1007/s40618-024-02392-5. https://pubmed.ncbi.nlm.nih.gov/38753296/

4. Sun, Hongwei, You, Yu, Guo, Mengmeng, Zhang, Yan, Ye, Shoudong. 2018. Tfcp2l1 safeguards the maintenance of human embryonic stem cell self-renewal. In Journal of cellular physiology, 233, 6944-6951. doi:10.1002/jcp.26483. https://pubmed.ncbi.nlm.nih.gov/29323720/