Fascin lysine 471 acetylation cooperates with serine 39 phosphorylation to inhibit actin‐bundling activity and tumor metastasis in esophageal squamous cell carcinoma

Abstract

Dear Editor, Fascin actin-bundling protein 1 (Fascin, gene name: FSCN1) is the primary actin-bundling protein that clusters filaments into stable and bundled filopodia [1]. In previous studies, elevated levels of Fascin promoted filopodia formation and enhanced the invasive ability of tumor cells, suggesting that Fascin is a target for therapeutic intervention [2,3]. Therefore, it is necessary to elucidate the detailed molecular mechanism by which Fascin bundles F-actin filaments.Rapid association/dissociation of Fascin from filaments is regulated by its post-translational modifications, such as the widely studied phosphorylation of conserved Ser-39 mediated by protein kinase C (PKC) [4]. The phosphorylation/dephosphorylation cycles of Ser-39 serve as a molecular switch to turn Fascin activity on or off to determine filopodia formation [5]. We previously reported that Fascin was acetylated by P300/CBP-associated factor (PCAF) on . We further elaborated on the precise regulatory mechanism of Fascin acetylation to inhibit its oncogenic function by reducing actin-bundling activity in esophageal squamous cell carcinoma (ESCC) cells, highlighting the