FNDC3B promotes cell migration and tumor metastasis in hepatocellular carcinoma

// Chin-Hui Lin 1 , Yao-Wen Lin 1 , Ying-Chun Chen 1 , Chen-Chung Liao 2 , Yuh-Shan Jou 3 , Ming-Ta Hsu 1 , Chian-Feng Chen 1 1 VYM Genome Research Center, National Yang-Ming University, Taipei, Taiwan 2 Proteomics Research Center, National Yang-Ming University, Taipei, Taiwan 3 Institutes of Biomedical Sciences, Academia Sinica, Taipei, Taiwan Correspondence to: Chian-Feng Chen, email: cfchen@ym.edu.tw Keywords: FNDC3B, hepatocellular carcinoma, metastasis Received: April 05, 2016      Accepted: June 13, 2016      Published: July 01, 2016 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.