Tfcp2l1-flox Mouse

Tfcp2l1, also known as CRTR-1 and LBP-9, is a transcription factor. It is crucial for maintaining the pluripotency and self-renewal of embryonic stem cells [1,3,6,8,9,10]. It is involved in multiple pathways related to cell fate determination and stemness regulation, and is of great biological importance in processes such as development and tissue regeneration [5]. Genetic models, especially KO/CKO mouse models, are valuable tools for studying its functions.

In renal medullary carcinoma, the loss of renal epithelial transcription factor TFCP2L1 is associated with the transformation of thick ascending limb cells into RMC cells, along with the gain of MYC and NFE2L2-associated oncogenic and ferroptosis resistance programs [2]. In hepatocellular carcinoma, knockdown of TFCP2L1 significantly reduced HCC cell proliferation, invasion, etc., while overexpression enhanced these functions, and it promotes the stemness of cancer stem cells through the NANOG/STAT3 pathway [3]. In thyroid cancer, decreased TFCP2L1 expression was associated with malignant clinicopathological characteristics, and its overexpression inhibited cell growth and motility [4]. In lung alveolar regeneration, Tfcp2l1 loss in adult alveolar epithelial type 2 (AT2) cells inhibits self-renewal and enhances AT2-AT1 differentiation during tissue regeneration [5]. In bladder cancer, the CDK1/TFCP2L1/ID2 cascade is involved in regulating bladder carcinogenesis, and TFCP2L1 downregulates ID2 by directly binding to its promoter region [7]. In mouse embryonic fibroblasts, hypoxia-induced Tfcp2l1 expression contributes to immortalization prior to malignant transformation [10].

In conclusion, Tfcp2l1 plays essential roles in maintaining stem cell pluripotency, self-renewal, and in processes like tissue regeneration. Its dysregulation is implicated in various cancers, including renal medullary carcinoma, hepatocellular carcinoma, thyroid cancer, and bladder cancer. Studies using KO/CKO mouse models have been instrumental in revealing its functions in these disease-related biological processes, providing insights into potential therapeutic targets.