Wasl, also known as the gene encoding neural Wiskott-Aldrich syndrome protein (N-WASP), is an actin nucleation promoting factor. It is involved in regulating actin polymerization, which is crucial for various cellular processes such as cell motility, phagocytosis, and vesicle trafficking. It functions through interacting with multiple binding partners and is associated with pathways like the p120-catenin/β-catenin/p21 pathway, and may also be involved in processes related to glycolysis, TNF-α signaling, mTOR signaling, and Wnt/β-catenin signaling [1,2].

In pancreatic ductal adenocarcinoma (PDAC), pancreas-specific Wasl deletion in two oncogenic Kras-based PDAC mouse models led to increased survival. This was due to either impaired tumor development with intact Trp53 or delayed tumor progression and a senescent phenotype upon Trp53 ablation. Loss of Wasl resulted in cell-autonomous senescence through displacement of binding partners, vesicular accumulation of certain proteins, and up-regulation of Cdkn1a(p21) [1].

In cervical cancer, lower expression of WASL was associated with lower pathological stage, and patients with high WASL expression had worse overall and recurrence-free survival. Knockdown of WASL was correlated with biological processes such as glycolysis, TNFα signaling, mTOR signaling, and Wnt/β-catenin signaling [2].

In conclusion, Wasl plays an oncogenic role in PDAC and cervical cancer as revealed through gene knockout-based research. Its function in regulating actin polymerization and involvement in various signaling pathways are essential for normal cellular processes, and its dysregulation contributes to cancer development. Mouse models with Wasl deletion have provided valuable insights into its role in these disease conditions, facilitating a better understanding of disease mechanisms and potentially guiding the development of new therapeutic strategies [1,2].