FSCN1 predicts survival and is regulated by a PI3K‐dependent mechanism in renal cell carcinoma

Abstract

While overexpression of FSCN1 is reported in several cancers, the prognostic significance of FSCN1 in renal cell carcinoma (RCC) and the molecular mechanisms involved remain largely unclear. We retrospectively enrolled 194 patients with non-metastatic clear-cell RCC undergoing nephrectomy in our center between 2008 and 2011. FSCN1 expression was assessed by immunohistochemical staining and its association with clinicopathologic features and survival were evaluated. Functional effects of a modulated FSCN1 expression were analyzed with regard to invasion in RCC cell lines and metastasis in vivo. Here, we reported that FSCN1 was up-regulated in RCC tissues compared to non-tumor tissues, and associated with poor overall survival and recurrence-free survival. Its expression was not associated with age, tumor size, and clinical TNM stage. The incorporation of FSCN1 into the T stage and histologic grade would help to refine individual risk stratification. Preclinical studies using multiple RCC cells and orthotopic xenografts mice model indicated that FSCN1 could promote RCC cell invasion in vitro, and metastasis in vivo. Mechanistically, overexpression of FSCN1 led to an up-regulation of MMP9 and N-Cadherin. Notably, treating RCC cells with PI3 K/AKT inhibitors or knockdown GSK-3β decreased the expression of FSCN1, and then attenuated RCC invasion. Together, our results demonstrate that FSCN as an oncogene is a potential novel prognostic biomarker for RCC patients after nephrectomy, and can promote RCC metastasis.

FSCN1 Promotes Epithelial-Mesenchymal Transition Through Increasing Snail1 in Ovarian Cancer Cells

“…Overexpression of FSCN1 promoted migration and invasion of cancer cells [11,12,[14][15][16][25][26][27], and was associated with clinically unfavorable phenotypes in human epithelial cancers including EOC [10,17,27,28] . Nevertheless, the correlation of FSCN1 with EMT was unkown.…”

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

“…To evaluate the effects of FSCN1 on tumor spreading in a physiologically faithful microenvironment, several studies performed orthotopic transplantation of cancer cell lines into the corresponding organs of athymic nude mice. 10,55,120,129 Downregulation of FSCN1 expression in prostate cancer cells DU145 10 or renal cancer cells 786-O 120 was shown to suppress tumor metastases in nude mice, whereas the overexpression of FSCN1 in osteosarcoma SaOS-2 cells enhanced lung metastasis in severe combined immunodeficiency (SCID) mice. The injection of cancer cells with FSCN1 knockdown into the abdominal cavities of nude mice suppressed metastatic tumor nodes when compared to those injected with control cells.…”

MicroRNA‑145‑5p suppresses fascin to inhibit the invasion and migration of cervical carcinoma cells

“…in addition, FScn1 is an important mediator of TGF-β1-induced invasion and migration of kidney cancer cells (KCC) via ERK and JNK signaling pathways (29). FScn1 could act as an oncogene and a potential novel prognostic biomarker for patients with renal cell carcinoma (rcc) after nephrectomy, and can promote rcc metastasis (30). However, the signaling pathway of FScn1 involved in cc is still unclear and will be investigated in future studies.…”