Actr3, also known as Actin-related protein 3, is an essential component of the actin-related protein 2/3 complex. This complex is involved in regulating cell motility, epithelial mesenchymal transition (EMT), and plays a role in processes like microtubule-based motility and gene expression [2].

In a conditional knockout mouse model where the murine Actr3 gene was deleted, Actr3 was found essential for fibroblast viability and growth. Acute, tamoxifen-induced Actr3 deletion led to near-complete loss of functional Arp2/3 complex expression, abolished lamellipodia formation and membrane ruffling. However, cells showed enhanced cell spreading with numerous filopodia, along with compromised cell migration directionality [4]. In pancreatic ductal adenocarcinoma (PDAC), ACTR3 expression is increased. Knockdown of ACTR3 in PDAC cells inhibited their invasive and migratory capacity, altered F-actin distribution and EMT marker expression, suggesting it promotes cell migration and invasion via EMT [1]. In hepatocellular carcinoma (HCC), higher expression of ACTR3 was associated with worse overall and progression-free survival, and it was identified as an independent prognostic biomarker. It was also positively correlated with immune cell infiltration and involved in multiple cancer-related pathways [3].

In conclusion, Actr3 is crucial for maintaining normal cell functions such as motility and viability. Its dysregulation in diseases like PDAC and HCC emphasizes its significance in cancer development and progression. The use of gene knockout mouse models has provided valuable insights into its functions in these disease conditions, highlighting its potential as a therapeutic target and prognostic indicator.