Mass Spectrometric Analysis Identifies AIMP1 and LTA4H as FSCN1‐Binding Proteins in Laryngeal Squamous Cell Carcinoma

Abstract

Dysregulation of fascin actin‐bundling protein 1 (FSCN1) enhances cell proliferation, invasion, and motility in laryngeal squamous cell carcinoma (LSCC), while the mechanism remains unclear. Here, co‐immunoprecipitation and mass spectrometry is utilized to identify potential FSCN1‐binding proteins. Functional annotation of FSCN1‐binding proteins are performed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis. Furthermore, the protein–protein interaction network of FSNC1‐binding proteins is constructed and the interactions between FSCN1 and novel identified interacting proteins AIMP1 and LTA4H are validated. Moreover, the expression and functional role of AIMP1 and LTA4H in LSCC are investigated. A total of 123 proteins are identified as potential FSCN1‐binding proteins, and functional annotation shows that FSCN1‐binding proteins are significantly enriched in carcinogenic processes, such as filopodium assembly‐regulation and GTPase activity. Co‐IP/western blotting and immunofluorescence confirm that AIMP1 and LTA4H bind and colocalize with FSCN1. Furthermore, both AIMP1 and LTA4H are upregulated in LSCC tissues, and knockdown of AIMP1 or LTA4H inhibits LSCC cell proliferation, migration, and invasion. Collectively, the identification of FSCN1‐binding partners enhances understanding of the mechanism of FSCN1‐mediated malignant phenotypes, and these findings indicate that FSCN1 binds to AIMP1 and LTA4H might promote the progression of LSCC.

FSCN1 acts as a promising therapeutic target in the blockade of tumor cell motility: a review of its function, mechanism, and clinical significance

“…Loss-of-function studies showed that FSCN1 knockdown inhibited LSCC migration, invasion, and growth through the suppression of EMT 53 . Furthermore, Gao et al identified that FSCN1 binds with AIMP1 and LTA4H in LSCC, and their results suggested that AIMP1 and LTA4H were possible effectors involved in FSCN1-mediated malignant progression of LSCC 54 . In addition, expression of FSCN1 is higher in tongue squamous cell carcinoma (TSCC) tissues and cells than in adjacent non-carcinoma tissues and normal control cells.…”

Fascin actin-bundling protein 1 in human cancer: Promising biomarker or therapeutic target?

“…In addition to the above interaction partners, various proteins have been found to physiologically interact with FSCN1. [36][37][38][39][40][41] However, it has not been established if these interactions regulate the actinbundling activity of FSCN1.…”

Aminoacyl-tRNA synthetases of the multi-tRNA synthetase complex and their role in tumorigenesis

“…AIMP1 has been associated with poor survival in patients with head and neck squamous cell carcinoma [81] . In laryngeal squamous cell carcinoma AIMP1, in cooperation with leukotriene A4 hydrolase (LTA4H), promotes cell proliferation, migration, and invasion by binding fascin actin-bundling protein 1 [82] . As both full-length AIMP1 and its cleaved product EMAP II exhibit anti-cancer activities, strategies have been developed to improve the stability of the recombinant proteins, primarily by reducing aggregation [83] .…”