Adenomatous polyposis coli-binding protein end-binding 1 promotes hepatocellular carcinoma growth and metastasis

Abstract

This study was performed to determine the clinical significance of adenomatous polyposis coli (APC)-binding protein end-binding 1 (EB1) in hepatocellular carcinoma (HCC) and to characterize its biochemical role in comparison with previous reports. We performed immunohistochemical staining to detect EB1 expression in tissues from 235 patients with HCC and investigated its correlations with clinicopathological features and prognosis. We also investigated the roles of EB1 in cell proliferation, migration, and tumorigenesis in vitro and in vivo by siRNA-and CRISPR/Cas9-mediated modulation of EB1 expression in human HCC cell lines. The results showed that EB1 expression was significantly correlated with several important factors associated with tumor malignancy, including histological differentiation, portal vein invasion status, and intrahepatic metastasis. Patients with high EB1 expression in HCC tissue had poorer overall survival and higher recurrence rates than patients with low EB1 expression. EB1 knockdown and knockout in HCC cells reduced cell proliferation, migration, and invasion in vitro and inhibited tumor growth in vivo. Further, genes encoding Dlk1, HAMP, and SLCO1B3 that were differentially expressed in association with EB1 were identified using RNA microarray analysis. In conclusion, elevated expression of EB1 promotes tumor growth and metastasis of HCC. EB1 may serve as a new biomarker for HCC, and genes coexpressed with EB1 may represent potential targets for therapy.

Large-scale identification of RBP-RNA interactions by RAPseq refines essentials of post-transcriptional gene regulation

“…Since we profiled the MAPRE1-and STMN1-RNA interactomes in liver cancer cells (HepG2), we inspected the association with hepatocellular carcinoma (LIHC). MAPRE1 and STMN1 have been linked to promote liver cancer progression through mechanisms exerted by the canonical functions in cytoskeletal remodeling (Aiyama et al, 2020;Lu et al, 2018;Orimo et al, 2008;Wong et al, 2008). We found that upregulation of MAPRE1 and STMN1 gene expression correlated with the severity of the pathological stage and significantly decreased patient survival in LIHC patients (Figure 6E-F).…”

EB1 Restricts Breast Cancer Cell Invadopodia Formation and Matrix Proteolysis via FAK

“…Previous studies show that EB1 is required for persistent directional migration [ 33 , 52 ]. Although not addressed directly in this study, EB1 has been reported to be overexpressed in diverse cancer types and to have pro-invasive functions [ 53 , 54 , 55 , 56 ]. Migration and invasion through basal membranes are two distinct sequential steps of the metastatic process.…”