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

Abstract

Fascin actin-bundling protein 1 (FSCN1) is a highly conserved actin-bundling protein that cross links F-actin microfilaments into tight, parallel bundles. Elevated FSCN1 levels have been reported in many types of human cancers and have been correlated with aggressive clinical progression, poor prognosis, and survival outcomes. The overexpression of FSCN1 in cancer cells has been associated with tumor growth, migration, invasion, and metastasis. Currently, FSCN1 is recognized as a candidate biomarker for multiple cancer types and as a potential therapeutic target. The aim of this study was to provide a brief overview of the FSCN1 gene and protein structure and elucidate on its actin-bundling activity and physiological functions. The main focus was on the role of FSCN1 and its upregulatory mechanisms and significance in cancer cells. Up-to-date studies on FSCN1 as a novel biomarker and therapeutic target for human cancers are reviewed. It is shown that FSCN1 is an unusual biomarker and a potential therapeutic target for cancer.

Keywords: FSCN1; biomarker; cancer; metastasis; therapeutic target.

Graphical abstract

Figure 1

FSCN1 gene and protein structure, post-translational modifications, and interactions (A) Schematic of the FSCN1 gene that is located at chromosome 7p22.1 and is about 13.84 kb long, containing 5 exons (represented in black blocks). (B) Schematic diagram for human FSCN1 protein structure, post-translational modifications, and interactions. FSCN1 consists of four highly conserved β-trefoil domains. Actin-binding site 1 (ABS1) is located at the amino terminus, in the β-trefoil 1 domain between amino acids (aa) 33 and 47, whereas the ABS2 is predicted to locate at the carboxyl terminus, in the region near serine 274 (S274). Post-translational modification sites of FSCN1 are indicated below the FSCN1 structure: P, phosphorylation (in red) and S39 (in C); Ub, monoubiquitination (in blue) and lysine (K)247 and K250 (in C). FSCN1-interacting proteins that regulate its activity or function are represented above FSCN1 at their described binding site. (C) Surface presentation of the human FSCN1 (PDB: 3P53). The four β-trefoil domains are highlighted with different colors. Three ABSs (ABS1−3), identified from systematic mutagenesis studies, are also shown.

Figure 2

Expression of FSCN1 protein in different human cancer tissues The average positive rate of FSCN1 protein expression in different types of human cancer tissues is shown in the center of the figure.

Figure 3

Transcriptional regulation of FSCN1 in human cancer Multiple transcriptional factors bind to the promoter regions of the FSCN1 gene. Regulatory factors or signaling pathways that regulate FSCN1 expression by activating the transcriptional factors are also shown.

Figure 4

Regulation of FSCN1 expression by miRNAs and long-noncoding RNAs in different human cancers The body map of FSCN1 expression in tumors reproduced from Gene Expression Profiling Interactive Analysis (GEPIA).

Figure 5

Schematic representation of the known signaling pathways mediated by FSCN1 in human cancers