FOS-like antigen 1 (FOSL1) (FOSL1)

FOS-like antigen 1 (FOSL1), also known as Fra-1, is a transcription factor and a key member of the Activator Protein-1 (AP-1) complex [1, 3]. It functions by heterodimerizing with JUN family proteins to bind DNA and regulate the expression of genes involved in cell proliferation, differentiation, and transformation [1, 3, 11]. FOSL1 is particularly significant in oncology as a major downstream effector of the RAS-ERK signaling pathway, where it drives the epithelial-mesenchymal transition (EMT) and promotes tumor invasion, metastasis, and chemoresistance [3, 11, 19]. It is frequently overexpressed in a wide range of solid tumors, including breast, lung, and colorectal cancers, and its high expression is strongly correlated with poor patient prognosis [1, 4, 10]. While traditionally considered "undruggable" due to its lack of a defined small-molecule binding pocket, FOSL1 is an emerging therapeutic target being addressed through novel strategies such as RNA interference, PROTAC-mediated degradation, and peptide-based inhibitors [6, 11, 12]. Additionally, indirect targeting via MEK/ERK inhibitors or HDAC inhibitors has shown efficacy in reducing FOSL1-mediated oncogenic activity [4, 11, 15].

Other names

Fra-1Fos-related antigen 1FOSL1AP-1 transcription factor subunit

Inhibition of AP-1 DNA binding activity, downregulation of FOSL1 mRNA expression, or induction of FOSL1 protein degradation.