Avil-flox Mouse

Avil, also known as advillin, is an actin-binding protein. It plays a role in many cytoskeletal functions and is involved in critical cell infrastructure. It may function as a converging node upstream of oncogenic pathways like PAX3-FOXO1 and RAS [1,2].

In rhabdomyosarcoma (RMS), AVIL is overexpressed in many RMS cell lines, patient-derived xenograft models, and clinical samples of both alveolar (ARMS) and embryonal (ERMS) subtypes. Genetic modulation experiments show that overexpression of AVIL in mesenchymal stem cells induces neoplastic transformation both in vitro and in vivo, and reversing overexpression reverses the transformation. Silencing AVIL in RMS cells nearly eradicates them in culture and inhibits in vivo xenograft growth in mice, while gain-of-function manipulations lead to increased cell growth and migration [1,2].

In conclusion, Avil is a key actin-binding protein with important functions in cytoskeletal regulation. In the context of RMS, studies using genetic modulation (akin to loss-of-function and gain-of-function models) have revealed its critical role in tumorigenesis and maintenance, suggesting it could be a potential target for treating this pediatric soft-tissue cancer.