Fmnl3-KO Mouse

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 multiple cellular functions such as polarity control, invasion, and migration [1,4,8]. It may be involved in pathways related to cell-cell adhesion, cytoskeletal mediation, and epithelial-to-mesenchymal transition (EMT), and is of great importance in normal cell function and disease-related processes. Genetic models, like gene knockout mouse models, are valuable for studying its functions.

In mouse oocytes, FMNL3 depletion leads 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 FASCIN to regulate actin filaments during oocyte meiosis [1]. In cancer research, FMNL3 is overexpressed in pancreatic cancer, predicting an immuno-hot phenotype and higher responses to anti-cancer therapies [2]. In nasopharyngeal carcinoma, high FMNL3 expression promotes cell metastasis via TGF-β1-induced EMT [3]. In tongue squamous cell carcinoma, FMNL3 overexpression is related to metastasis and poor prognosis, and its silencing inhibits cell migration and invasion [5]. In breast cancer, FMNL3 promotes cell migration and invasion by inhibiting Rad23B-induced ubiquitination of Twist1 [6]. In melanoma, inhibition of FMNL3 affects cell morphology and migration [7].

In conclusion, FMNL3 is essential for actin-mediated processes such as spindle migration and cytokinesis in oocytes. In disease, especially cancer, FMNL3 is involved in metastasis, prognosis, and immune-related phenotypes. Studies using KO/CKO mouse models and other functional studies have provided insights into its role in these biological processes and disease conditions, which may contribute to a better understanding of disease mechanisms and potential therapeutic strategies.