Fmnl1, or Formin-like 1, belongs to the formin protein family responsible for cytoskeletal remodeling. It has been implicated in various cellular processes, such as cell migration, proliferation, and invasion, by interacting with signaling pathways like CXCR2, TGF-β1/SMADs, and Rac1 [1-3]. Fmnl1 is expressed in multiple cell types, including hematopoietic cells, T cells, and cancer cells, and is crucial for normal immune function and has significant implications in cancer progression. Genetic models, including gene-knockout (KO) models, are valuable for studying its functions.

In cancer, FMNL1 depletion in multiple cancer cell lines and in vivo models has shown significant impacts. In clear cell renal cell carcinoma (ccRCC), FMNL1 upregulation promotes metastasis via induction of CXCR2, and high expression is associated with poor prognosis. Knockdown of FMNL1 inhibits cell migration in vitro and tumor metastasis in vivo [1]. In non-small cell lung cancer (NSCLC), reducing FMNL1 expression suppresses cell proliferation, migration, invasion, and bone metastasis by reducing TGF-β1 expression [2]. In leukemia cells, FMNL1 depletion decreases cell proliferation, colony formation, migration, and tumor growth of xenografts, and its silencing increases Rac1 activity [3]. In nasopharyngeal carcinoma, depletion of FMNL1 suppresses invadopodia formation, epithelial-mesenchymal transition (EMT), and invasive/metastatic capacities [4]. In glioblastoma multiforme, FMNL1 downregulation suppresses cell migration and invasion, actin fiber assembly, and is an independent predictor of poor prognosis [5]. In breast adenocarcinoma, suppression of FMNL1 protein expression impairs cell adhesion, migration, and invasion [6].

In conclusion, Fmnl1 plays essential roles in cell migration, proliferation, and invasion, with significant implications in cancer progression. KO and other loss-of-function models have been instrumental in revealing these roles, highlighting Fmnl1 as a potential prognostic factor and therapeutic target in multiple cancer types. Additionally, Fmnl1 is associated with T cell migration in the immune system, indicating its broader importance in biological processes [1-4, 6, 7, 9].