Anti-SOX4 monoclonal antibody, clone 265D5b

PUMA is a crucial regulator of apoptotic cell death mediated by p53-dependent and p53-independent mechanisms. In many cancer cells, PUMA expression is induced in response to DNA-damaging reagent in a p53-dependent manner. However, few studies have investigated transcription factors that lead to the induction of PUMA expression via p53-independent apoptotic signaling. In this study, we found that the transcription factor Sox4 increased PUMA expression in response to trichostatin A (TSA), a histone deacetylase inhibitor in the p53-null human lung cancer cell line H1299. Ectopic expression of Sox4 led to the induction of PUMA expression at the mRNA and protein levels, and TSA-mediated up-regulation of PUMA transcription was repressed by the knockdown of Sox4. Using luciferase assays and chromatin immunoprecipitation, we also determined that Sox4 recruits p300 on the PUMA promoter region and increases PUMA gene expression in response to TSA treatment. Taken together, these results suggest that Sox4 is required for p53-independent apoptotic cell death mediated by PUMA induction via TSA treatment. Crown Copyright (C) 2013 Published by Elsevier Inc. All rights reserved.

Recurrence of hepatocellular carcinoma (HCC) even after curative resection causes dismal outcomes of patients. Here, to delineate the driver events of genomic and transcription alteration during HCC recurrence, we performed RNA-Seq profiling of the paired primary and recurrent tumors from two patients with intrahepatic HCC. By comparing the mutational and transcriptomic profiles, we identified somatic mutations acquired by HCC recurrence including novel mutants of GOLGB1 (E2721V) and SF3B3 (H804Y). By performing experimental evaluation using siRNA-mediated knockdown and overexpression constructs, we demonstrated that the mutants of GOLGB1 and SF3B3 can promote cell proliferation, colony formation, migration, and invasion of liver cancer cells. Transcriptome analysis also revealed that the recurrent HCCs reprogram their transcriptomes to acquire aggressive phenotypes. Network analysis revealed CXCL8 (IL-8) and SOX4 as common downstream targets of the mutants. In conclusion, we suggest that the mutations of GOLGB1 and SF3B3 are potential key drivers for the acquisition of an aggressive phenotype in recurrent HCC.