Fmnl3, or Formin-like 3, is a member of the formin-likes within the formin family. As an F-actin nucleator, it is crucial for functions such as polarity control, invasion, and migration [1]. It is involved in pathways related to cell-cell adhesion, cytoskeletal mediation, and may be associated with tumorigenesis pathways [1,2,3].

In mouse oocytes, FMNL3 depletion led to polar body extrusion failure and symmetric meiotic division, with spindle migration defects at late metaphase I likely due to decreased cytoplasmic actin. FMNL3 interacts with the actin-binding protein FASCIN to regulate actin filaments during oocyte meiosis [1]. In cancer research, FMNL3 is overexpressed in pancreatic cancer, nasopharyngeal carcinoma, tongue squamous cell carcinoma, and breast cancer, promoting cell metastasis, invasion, and associated with poor prognosis. For example, in nasopharyngeal carcinoma, TGF-β1/FMNL3 signalling may mediate epithelial-to-mesenchymal transition (EMT) related to metastasis [1,2,4,5]. In melanoma, inhibition of FMNL3 affected cell morphology and migration [6].

In summary, Fmnl3 is essential for actin-mediated processes like spindle migration and cytokinesis in oocytes. In disease, especially cancer, Fmnl3 is often overexpressed, promoting metastasis and invasion. Studies using gene knockout or conditional knockout models in mice and cell-based loss-of-function experiments have been crucial in revealing these functions, helping understand the biological mechanisms underlying oocyte development and cancer progression.