GRHL2

GRHL2 is a transcription factor that plays a central role in epithelial cell fate determination, epithelial development, and maintenance of epithelial identity through regulation of epithelial gene expression programs^[4][1]. Mechanistically, GRHL2 functions as a key suppressor of epithelial-mesenchymal transition (EMT) by promoting epithelial junctional components, including E-cadherin and claudins, while repressing EMT-associated regulators such as ZEB1^[5][2]. Through this EMT-regulatory network, GRHL2 contributes to epithelial morphogenesis and preservation of epithelial phenotypes in multiple biological contexts^[4][5][6]. In cancer models, GRHL2 expression is closely associated with epithelial status, and genetic silencing of GRHL2 induces partial EMT in lung cancer and normal epithelial cell models, supporting its role in maintaining epithelial characteristics^[6]. Studies in colorectal cancer further demonstrate that the GRHL2/ZEB1 axis suppresses EMT-associated migration, invasion, and metastatic progression^[7]. GRHL2 is also implicated in breast cancer biology, where it contributes to determination of the epithelial phenotype and influences tumor progression-related processes^[8]. Compared with related Grainyhead family members, GRHL2 is recognized as a major regulator of epithelial cell identity and EMT/MET plasticity, making it a widely used experimental target for studies of epithelial differentiation, tumor cell plasticity, and metastatic mechanisms^[1][3]. No well-established GRHL2-selective agonists or inhibitors were identified in the retrieved literature; therefore, functional investigation primarily relies on genetic overexpression or silencing approaches^[6][7].

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