Fmnl1-flox Mouse

Fmnl1, formin-like 1, belongs to the formin family and is responsible for cytoskeletal remodeling, playing a role in various biological processes including cell migration, proliferation, and the immune response [1,2,3,5,6,7,9]. It is involved in multiple signaling pathways such as those related to CXCR2, TGF-β1, and Rac1 [1,3,7].

In cancer, FMNL1 has been extensively studied. In clear cell renal cell carcinoma (ccRCC), its upregulation promotes metastasis via induction of CXCR2, and high expression correlates with advanced tumor stage and poor prognosis [1]. In nasopharyngeal carcinoma (NPC), high FMNL1 expression is associated with aggressive disease, and it enhances cell aggressiveness by epigenetically upregulating MTA1 [2]. In non-small cell lung cancer (NSCLC), reducing FMNL1 expression suppresses cell proliferation, migration, invasion, and bone metastasis by reducing TGF-β1 expression [3]. In leukemia cells, FMNL1 depletion reduces cell proliferation, colony formation, and migration [7]. In glioblastoma multiforme (GBM), FMNL1 is an independent predictor of poor prognosis, and its downregulation suppresses cell migration and invasion [6]. In breast adenocarcinoma, FMNL1 is required for efficient cell migration, and its γ-isoform enhances cell adhesion and migration by bundling filamentous actin [9]. In gastric cancer, elevated FMNL1 is associated with larger tumor size and higher disease stage [10]. Also, FMNL1 is a biomarker for tumor-infiltrating immune cells and is associated with a good immunotherapeutic response [4].

In T cells, FMNL1 contributes to efficient migration by promoting deformation of the rigid T cell nucleus in confined environments [5]. In membranous nephropathy and other glomerular diseases, anti-FMNL1 IgG4 antibodies are found, which may be related to disease progression [8].

In conclusion, FMNL1 is crucial for cytoskeletal remodeling and has significant impacts on cancer progression, immune cell function, and disease processes in various tissues. Studies using gene knockdown and other loss-of-function models have revealed its role in promoting cancer cell migration, invasion, and proliferation, highlighting its potential as a prognostic factor and therapeutic target in multiple cancers.