Abstract
Emerging evidence indicates that Fascin-1 (FSCN1) may possess a causal role in the development of several types of cancers and serves as a novel biomarker of aggressiveness in certain carcinomas. However, the regulatory mechanism of FSCN1 in triple-negative breast cancer (TNBC) cell invasion and migration is still largely unknown. In our study, we observed that the FSCN1 expression rates were significantly higher in invasive ductal carcinoma, compared with both usual ductal hyperplasia and ductal carcinoma in situ. FSCN1 expression was significantly higher in cases of TNBC compared with the non-TNBC subtype. Overexpression of FSCN1 promoted TNBC cell migration and invasion. Epidermal growth factor induced the expression of FSCN1 through activation of MAPK, which subsequently promoted cell migration and invasion. A significant decrease in FSCN1 expression following the co-treatment of FSCN1 siRNA and Gefitinib, compared with the separate treatment of FSCN1 siRNA or Gefitinib. Furthermore, we found that there was a significant association between FSCN1 expression and poor relapse-free survival and overall survival. Therefore, we suggest that co-targeting epidermal growth factor receptor and FSCN1 dual biomarker may be used as a novel therapeutic strategy for TNBC.
Highlights
Fascin-1 (FSCN1) is an actin-bundling protein, and its enhanced expression levels have been reported in several types of carcinomas, including that of the lung[7], colon[8], stomach[9], ovary[10], and breast[11]
We observed that FSCN1 expression was significantly higher in cases of triple-negative breast cancer (TNBC) (88.6%, 62/70) compared with the non-TNBC subtype (19.2%, 71/370) (P < 0.0001) (Table 2), which is indicative that FSCN1 expression is associated with TNBC
We observed that the expression levels of FSCN1 were significantly higher in patients with invasive ductal carcinoma (IDC), compared with those in patients with usual ductal hyperplasia (UDH) and ductal carcinoma in situ (DCIS)
Summary
Fascin-1 (FSCN1) is an actin-bundling protein, and its enhanced expression levels have been reported in several types of carcinomas, including that of the lung[7], colon[8], stomach[9], ovary[10], and breast[11]. FSCN1 expression is associated with hormone receptor-negative, more aggressive clinical course, and associated with TNBC in African American and Chinese women[11,12,13]. The mechanism underlying the effect of FSCN1 in the development of breast cancer, especially on TNBC, is yet to be elucidated. We used immunohistochemical (IHC) analysis to detect FSCN1 expression in a series of paraffin-embedded breast lesion tissue, including that from usual ductal hyperplasia (UDH), ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (IDC), and analyzed the relationship between FSCN1 and TNBC or epidermal growth factor receptor (EGFR). We further described the potential mechanism by which FSCN1 contributes to TNBC cell migration and invasion. We demonstrated that EGF induced the expression of FSCN1 through MAPK activation, subsequently promoting cell migration and invasion. We found there to be a significant decrease in FSCN1 expression following the co-treatment of FSCN1 siRNA and Gefitinib, compared with the separate treatment of FSCN1 siRNA or Gefitinib
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