FNDC3B promotes cell migration and tumor metastasis in hepatocellular carcinoma.

Chin-Hui Lin,Yao-Wen Lin,Chian-Feng Chen,Yuh-Shan Jou,Chen-Chung Liao,Ying-Chun Chen,Ming-Ta Hsu

doi:10.18632/oncotarget.10374

Abstract

Recurrence and metastasis are common in hepatocellular carcinoma (HCC) and correlate with poor prognosis. We investigated the role of fibronectin type III domain containing 3B (FNDC3B) in HCC metastasis. Overexpression of FNDC3B in HCC cell lines enhanced cell migration and invasion. On the other hand, knockdown of FNDC3B using short-hairpin RNA reduced tumor nodule formation in both intra- and extra-hepatic metastasis. High levels of FNDC3B were observed in metastatic HCCs and correlated with poor patient survival and shorter recurrence time. Mutagenesis and LC-MS/MS analyses showed that FNDC3B promotes cell migration by cooperating with annexin A2 (ANXA2). Furthermore, FNDC3B and ANXA2 expression correlated negatively with patient survival. Our results indicate that FNDC3B behaves like an oncogene by promoting cell migration. This suggests FNDC3B could serve as a biomarker and therapeutic target for HCC metastasis.

Highlights

Hepatocellular carcinoma (HCC) is one of the most common and aggressive tumors worldwide [1, 2]
We performed in vitro cell migration and invasion assays, in vivo metastasis assays, tissue array analyses, and survival analyses of patients to study the role of fibronectin type III domain containing 3B (FNDC3B) in hepatocellular carcinoma (HCC) metastasis
Clinical data indicated that the expression of FNDC3B correlated positively with HCC metastasis and negatively with patient survival

Summary

Introduction

Hepatocellular carcinoma (HCC) is one of the most common and aggressive tumors worldwide [1, 2]. In spite of therapeutic advancements that can extend the lifespan of patients [2], HCC is still the third leading cause of cancer-related deaths in the world [3]. A genome-wide approach to identify common copy number alternation regions in the genome, targeting either amplifications or deletions, can reveal novel cancer genes. We screened for genomic aberrations in HCC cell lines and identified a 329 kb amplicon in 3q26.3 containing only 1 gene, fibronectin type III domain containing 3B (FNDC3B), which was upregulated in HCC tissues and cell lines [7]. The knockdown of FNDC3B decreased anchorage independent growth (AIG) and tumor formation in xenograft models [7]

Methods

Results

Conclusion