Increased expression of formin-like 3 contributes to metastasis and poor prognosis in colorectal carcinoma.

Abstract

Formin-like 3 (FMNL3), a member of diaphanous-related formins subfamily, plays an important role in cytoskeleton reorganization, cell adhesion and cancer cell invasion in vitro. This study aimed to explore the expression of FMNL3 in colorectal carcinoma (CRC) cell-lines and tissues, and further evaluate its prognostic value and correlation with the clinicopathological parameters, and also investigate the effects of FMNL3 gene silencing on the growth and metastasis of CRC in vivo. Immunohistochemical analysis showed that FMNL3 protein was distributed in a punctuate aggregation pattern and located mainly in the cytoplasm of glandular cavity side, close to the nucleus of CRC cells. The positive rate of FMNL3 expression was 87.5% (84/96) in CRC, which was significantly higher than that in adjacent normal mucosa (30%, 9/30). Moreover, FMNL3 protein expressed far more in primary CRC with metastasis and corresponding lymph nodes metastatic CRC than in primary CRC without metastasis. Increased expression of FMNL3 was closely correlated with tumor size, differentiation, serosal invasion, and both lymph node metastasis and distant metastasis. However, it was not correlated with patients' age and gender. According to Kaplan-Meier survival analyses, patients with FMNL3 high expression level had lower overall survival rate than that with FMNL3 low expression level. Univariate and multivariate analyses revealed that high FMNL3 expression was a significant and independent prognostic predictor of patients with CRC. In addition, FMNL3 mRNA and protein levels were substantially up-regulated in CRC-metastasis-derived cell lines, as compared to those in primary-CRC-derived ones. FMNL3 gene silencing suppressed the growth and metastasis of CRC in vivo. In conclusion, FMNL3 plays an important role in the progression and metastasis of CRC and may be a novel potential prognostic predictor and therapeutic target for patients with CRC.