Fascin promotes migration and invasion and is a prognostic marker for oral squamous cell carcinoma

Abstract

Oral squamous cell carcinoma (OSCC) prognosis is related to clinical stage and histological grade. However, this stratification needs to be refined. We conducted a comparative proteome study in microdissected samples from normal oral mucosa and OSCC to identify biomarkers for malignancy. Fascin and plectin were identified as differently expressed and both are implicated in several malignancies, but the clinical impacts of aberrant fascin and plectin expression in OSCCs remains largely unknown. Immunohistochemistry and real-time quantitative PCR were carried out in ex vivo OSCC samples and cell lines. A loss-of-function strategy using shRNA targeting fascin was employed to investigate in vitro and in vivo the fascin role on oral tumorigenesis. Transfections of microRNA mimics were performed to determine whether the fascin overexpression is regulated by miR-138 and miR-145. We found that fascin and plectin are frequently upregulated in OSCC samples and cell lines, but only fascin overexpression is an independent unfavorable prognostic indicator of disease-specific survival. In combination with advanced T stage, high fascin level is also an independent factor of disease-free survival. Knockdown of fascin in OSCC cells promoted cell adhesion and inhibited migration, invasion and EMT, and forced expression of miR-138 in OSCC cells significantly decreased the expression of fascin. In addition, fascin downregulation leads to reduced filopodia formation and decrease on paxillin expression. The subcutaneous xenograft model showed that tumors formed in the presence of low levels of fascin were significantly smaller compared to those formed with high fascin levels. Collectively, our findings suggest that fascin expression correlates with disease progression and may serve as a prognostic marker and therapeutic target for patients with OSCC.

Evaluation of Fascin Expression in Selected Salivary Gland Tumors (An immunohistochemical study)

“…Regarding adenoid cystic carcinoma, fascin was seen in cytoplasm and nucleus of malignant cells where solid pattern showing higher expression (64.61) than tubular (47.27) and cribriform patterns (41.83). These results are in accordance with those who found that the increased expressions of fascin are correlated with the high-grade ACC (17) , as fascin overexpression is linked with improved proliferation, cell motility, high possible for invasion and metastasis. Fascin allow cancer cells to invade into the matrix (26,31) .…”

“…Fascin expression showed the statistically significant higher value of area percent in malignant tumors (MEC and ACC) (55.45) than benign tumors (PA and Warthin's tumors (34.01); meanwhile, the normal salivary gland tissue showed the statistically significant least value (16.72). These results were in accordance with the study which found that the immunohistochemical appearance of fascin in malignant types of salivary gland tumor was meaningfully greater than that in normal salivary gland tissue (17) .…”

Correlation between the Expression of Interleukin-6, STAT3, E-Cadherin and N-Cadherin Protein and Invasiveness in Nonfunctional Pituitary Adenomas

“…Machesky and Li found that the high expression of Fascin protein is positively correlated with the low expression of E-cadherin; Fascin protein can induce the occurrence of EMT and knocking out Fascin protein can inhibit the occurrence of EMT and tumor invasion. [25][26][27] Our study also found that Fascin expression in IPA was higher than that in NIPA, and the expression level was positively correlated with Knosp's imaging classification. 28 Thus, Fascin may be an important protein marker that causes pituitary adenomas to invade the periphery.…”

Clinicopathological significance of miR‐26, miR‐107, miR‐125b, and miR‐203 in head and neck carcinomas

“…The expression levels of miR‐26, miR‐107, miR‐125b, and miR‐203 were initially measured by qRT‐PCR in 32 primary HNSCC divided into two groups: 16 with lymph node metastasis and 16 without metastasis. The expression values of intended microRNAs were normalized with a corresponding mean value of the endogenous RNU48, a small nucleolar RNA that has been shown to be a good quality control and reference maker of microRNA expression analysis (Bufalino et al., ; Rodrigues et al., ). Only samples showing abundance and stable expression of the internal control RNU48 were included in this study.…”