FNDC3B promotes cell migration and tumor metastasis in hepatocellular carcinoma

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.

FNDC3B 3′‐UTR shortening escapes from microRNA‐mediated gene repression and promotes nasopharyngeal carcinoma progression

“…FNDC3B , also known as FAD104 (factor for adipocyte differentiation 104), is located at 3q26, and is amplified in more than 20% of human tumors 24,25 . Recently, FNDC3B was found to serve as an oncogene and it can promote tumorigenesis and metastasis in various cancer types 24‐28 . FNDC3B can promote cell migration and metastasis by cooperating with annexin A2 (ANXA2) in hepatocellular carcinoma 26 .…”

Clinical Significance and Prognostic Value of the Expression of Fibronectin Type III Domain Containing 3B in Pancreatic Carcinoma

“…Many studies have con rmed that FNDC3B promotes tumor progression. Lin et al found that FNDC3B enhances the migration and metastasis of hepatocellular carcinoma cells by binding to annexin A2 (ANXA2) through the FNIII1-4 domain [14]. Cai et al con rmed that FNDC3B increases the proliferation of liver cancer cells by inducing epithelial to mesenchymal transition (EMT) to activate the PI3K / AKT, Rb1 and TGF-β pathways [28].…”

“…Fibronectin type III domain containing 3B (FNDC3B), is a protein of the FNDC3 family that includes FNDC3A, FNDC3B and FNDC3C, also known as factor for adipocyte differentiation 104 (FAD104), it contains a proline-rich region, and 9 bronectin type III structures domain and a transmembrane region, and is a regulator of adipocyte and osteoblast differentiation [8][9][10][11][12]. Fibronectin type III (FNIII) domain of FNDC3B serves as a tail sheath, integrates with different proteins, and plays an important role in cell adhesion and growth signaling [9,13,14]. Homozygous disruption of FNDC3B causes mice to die at birth from abnormalities in the lungs [14,15], and has a signi cant effect on the adhesion, proliferation and migration of mouse embryonic broblasts [9,16].…”

“…Fibronectin type III (FNIII) domain of FNDC3B serves as a tail sheath, integrates with different proteins, and plays an important role in cell adhesion and growth signaling [9,13,14]. Homozygous disruption of FNDC3B causes mice to die at birth from abnormalities in the lungs [14,15], and has a signi cant effect on the adhesion, proliferation and migration of mouse embryonic broblasts [9,16]. Cell adhesion is important in tumorigenesis because it provides tumor cells with the necessary contacts and cell-matrix interactions needed for cell signaling, proliferation, and migration [17].…”

Pax-5 Inhibits Breast Cancer Proliferation Through MiR-215 Up-regulation

“…It is important to note that most of the miR-215-targeted genes have oncogenic properties which corresponds to the tumor suppressive role of Pax-5 in breast cancer cells (41)(42)(43)(44)(45)(46). For example, Fibronectin type III domain containing 3B gene (FNDC3B) located at the 3q26 locus is amplified in 20% of tumors and plays an oncogenic role in many cancers (41,47). Additionally, activated leukocyte cell adhesion molecule (ALCAM) is implicated in cell to cell interactions and inhibits breast cancer apoptosis (43).…”