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

• Published in: Cancer communications (London, England) England), 2022-07, Vol.42 (7), p.668-672
• Main Authors: Zeng, Fa‐Min, Cheng, Yin‐Wei, He, Jian‐Zhong, Xu, Xiu‐E, Liao, Lian‐Di, Xu, Li‐Yan, Li, En‐Min
• Format: Article
• Language: English
• Subjects: Cytokeratin; Esophageal cancer; Kinases; Letter to the Editor; Letters to the Editor; Lymphatic system; Metastasis; Phosphorylation; Plasmids; Proteins; Tumors
• ISSN: 2523-3548; 2523-3548
• DOI: 10.1002/cac2.12297

List of abbreviations A alanine AcK471-Fascin Fascin-K471 acetylation CK cytokeratin D aspartic acid DFS disease-free survival ESCC esophageal squamous cell carcinoma FascinS39A/K471Q a mimic of phosphorylation defective and hyperacetylated Fascin FascinS39A/K471R a mimic of phosphorylation and acetylation defective Fascin FascinS39D/K471Q a mimic of hyperphosphorylation and hyperacetylated Fascin FascinS39D/K471R a mimic of hyperphosphorylation and acetylation defective Fascin FRAP fluorescence recovery after photobleaching G/F-actin ratio ratio of G-actin to F-actin GFP Green fluorescent protein H&E hematoxylin and eosin IHC immunohistochemistry Lys-471 lysine 471 OS overall survival P pellet PCAF P300/CBP-associated factor PhoS39-Fascin Fascin-S39 phosphorylation PKC protein kinase C PTMs posttranslational modifications S supernatant Ser-39 Serine 39 SHEEC Shantou Human Embryonic Esophageal Carcinoma Thr-403 Threonine 403 TMAs tissue microarrays TNM tumor-node-metastasis WT wild-type Dear Editor, Fascin actin-bundling protein 1 (Fascin, gene name: 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]. [...]it is necessary to elucidate the detailed molecular mechanism by which Fascin bundles F-actin filaments. Time-lapse imaging showed that WT Fascin, but not FascinS39D/K471Q and FascinS39A/K471Q, could restore filopodia lifetime (Supplementary Figure S2B). [...]expression of the deacetylated and dephosphorylated mutant (S39A/K471R) led to long, persistent filopodia with an increased lifetime (Supplementary Figure S2B). Previous studies have suggested that monomeric proteins move more rapidly than proteins with short transient interactions, whereas proteins with long transient interactions move the slowest [ 7]. [...]our data indicated that at the base of the