Ebp1 p48 promotes oncogenic properties in hepatocellular carcinoma through p38 MAPK/HIF1α activation and p53 downregulation.

Abstract

The ErbB3 binding protein 1 (Ebp1) has been reported in several cancers, in which it can act as either a pro-oncogenic regulator or a tumor suppressor. However, the biological function and molecular mechanism of Ebp1 p48 in hepatocellular carcinoma (HCC) remain unclear. Here, we report that the long isoform of Ebp1, p48, is highly expressed in HCC tissues compared with normal tissues. Ebp1 p48 expression was correlated with the tumor size in HCC patients. Silencing Ebp1 p48 by transduction with lentiviral shEbp1 dramatically reduced the proliferation rate, soft agar colony generation, and tumor formation in vivo. We further demonstrated that Ebp1 p48 knockdown resulted in decreased p38 phosphorylation, which subsequently reduced hypoxia-inducible factor 1α (HIF1α) expression. Moreover, Ebp1 p48 knockdown led to an upregulation of p53 expression through MDM2 downregulation. Taken together, these results suggest that the Ebp1/p38/HIF1α signaling pathway and the Ebp1-mediated downregulation of p53 are involved in hepatocarcinogenesis. Therefore, Ebp1 and its downstream signaling pathways may be promising therapeutic targets of HCC.

• Authors: Yanqiu Bao, Munakarmi Suvesh, Xiaobo Li, Xin Bai, Hua Li, Xiangdan Li, Dongyuan Xu, Lan Liu
• Journal: Molecular carcinogenesis (Mol Carcinog) Vol. 60 Issue 4 Pg. 252-264 (04 2021) ISSN: 1098-2744 [Electronic] United States
• PMID: 33634940 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 Wiley Periodicals LLC.

Chemical References

• Adaptor Proteins, Signal Transducing
• HIF1A protein, human
• Hypoxia-Inducible Factor 1, alpha Subunit
• Imidazoles
• PA2G4 protein, human
• Protein Isoforms
• Pyridines
• RNA-Binding Proteins
• TP53 protein, human
• Tumor Suppressor Protein p53
• p38 Mitogen-Activated Protein Kinases
• SB 203580

Topics

• Adaptor Proteins, Signal Transducing (genetics, metabolism)
• Animals
• Carcinoma, Hepatocellular (genetics, metabolism, pathology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Down-Regulation
• Female
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Hep G2 Cells
• Humans
• Hypoxia-Inducible Factor 1, alpha Subunit (metabolism)
• Imidazoles (pharmacology)
• Liver Neoplasms (genetics, metabolism, pathology)
• MAP Kinase Signaling System
• Male
• Mice
• Neoplasm Transplantation
• Protein Isoforms (genetics, metabolism)
• Pyridines (pharmacology)
• RNA-Binding Proteins (genetics, metabolism)
• Survival Analysis
• Tissue Array Analysis
• Tumor Suppressor Protein p53 (metabolism)
• p38 Mitogen-Activated Protein Kinases (metabolism)