Elevated expressions of fascin mRNA and protein in cancer cells have been correlated with aggressive clinical course, poor prognosis and shorter survival. Fascin is an evolutionarily conserved actin-binding protein that plays a key role in forming filopodia. It is reported that the lysine 471 residue (K471) of fascin can be acetylated and also involves in its actin binding, but the roles of K471 acetylation in filopodia formation are still uncertain. In this paper, we produced point mutants mimicking the active deacetylated (Lys471Arg, K471R) or inactive acetylated (Lys471Gln, K471Q) states of fascin. The actin-binding assay showed that the fascin K471Q mutation decreased the actin binding activity of fascin, compared with wild-type fascin (WT) and K471R mutant fascin in the esophageal cancer cells. Moreover, live imaging revealed that K471Q mutant fascin reduced the number and length of filopodia, whereas the K471R mutant increased filopodia frequency. The fascin K471Q mutation changed the straight filopodia became forniciform filopodia. The protrusion presented abnormal morphology when cells spread. Further functional experiments showed that the K471Q mutant fascin rendered the tumor cell migration, invasion and tumorigenesis decrease significantly, whereas K471R mutant fascin like WT fascin still maintained a strong ability. Taken together, we propose that the lysine K471 residue may be a key specific actin crosslinking site and also involved in the tumor biological function of fascin.
Citation Format: Fa-Min Zeng, Xiao-Ning Wang, Ying-Li Zhang, Lian-Di Liao, En-Min Li, Li-Yan Xu. Acetylation of Fascin on the lysine 471 residue produces a change in growth and mobility phenotype of esophageal cancer cells by inducing F-actin rearrangement. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4424.