WASF2, also known as Wiskott-Aldrich syndrome protein Verprolin-homologous protein 2 or WAVE2, is an integral member of the actin cytoskeleton pathway, playing a crucial role in cell motility, such as regulating actin reorganization during cell migration [1,3]. It is involved in multiple signaling pathways, including TGF-β signaling, Kras signaling, fatty acid metabolism, p53 pathways, and Wnt/β-catenin axis [1,4]. Genetic models can be valuable for studying its functions.

In various cancers, WASF2 shows different roles. In head and neck squamous cell carcinoma (HNSCC), hypermethylated WASF2 acts as a tumor suppressor. Its down-regulation in HNSCC tissues is related to elevated promoter methylation, and DNA methylation inhibitor can restore its mRNA expression. WASF2 expression is a favorable indicator for HPV-positive HNSCC, and its promoter methylation is detrimental to patient survival. Also, it is positively associated with tumor-killing immune cells [1]. In ovarian cancer, WASF2 is abnormally expressed, significantly correlated with overall survival and progression-free interval, and related to the tumor microenvironment, immune infiltration, TMB, MSI, and antitumor drugs sensitivity. Knockdown of WASF2 inhibits the proliferative, migratory and invasive capacity of ovarian cancer cells [2]. In hepatocellular carcinoma (HCC), WASF2 is overexpressed and hypomethylated, and its inactivation exerts anti-tumorigenic effects on HCC cells in vitro and in vivo [3]. In spinal cord glioma, EMX1 functions as a tumor inhibitor by suppressing WASF2-dependent activation of the Wnt/β-catenin axis [4].

In conclusion, WASF2 is essential in regulating cell motility through the actin cytoskeleton pathway. Its abnormal expression and epigenetic changes are closely associated with the development and prognosis of multiple cancers, such as HNSCC, ovarian cancer, HCC, and spinal cord glioma. Studies using various models help to understand its functions in these disease conditions, providing potential targets for cancer treatment.