The FBI1/Akirin2 target gene, BCAM, acts as a suppressive oncogene

PLoS One. 2013 Nov 6;8(11):e78716. doi: 10.1371/journal.pone.0078716. eCollection 2013.

Abstract

Basal cell adhesion molecule (BCAM), known to be a splicing variant of Lutheran glycoprotein (LU), is an immunoglobulin superfamily membrane protein that acts as a laminin α5 receptor. The high affinity of BCAM/LU for laminin α5 is thought to contribute to the pathogenesis of sickle red blood cells and to various developmental processes. However, the function of BCAM in carcinogenesis is poorly understood. Based on microarray expression analysis, we found that BCAM was one of the target genes of the oncogenic 14-3-3β-FBI1/Akirin2 complex, which acts as a transcriptional repressor and suppresses MAPK phosphatase-1 gene expression. To elucidate the detailed function of BCAM in malignant tumors, we established BCAM-expressing hepatoma K2 cells. These cells lost the malignant characteristics of parental cells, such as anchorage-independent growth, migration, invasion, and tumorigenicity. Moreover, luciferase reporter assays and chromatin immunoprecipitation analysis revealed that the 14-3-3β-FBI1/Akirin2 complex bound to the BCAM promoter and repressed transcription. Thus, these data indicate that BCAM is a suppressive oncoprotein, and that FBI1/Akirin2 is involved in tumorigenicity and metastasis of hepatoma through the downregulation of suppressive oncogenes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 14-3-3 Proteins / genetics*
  • 14-3-3 Proteins / metabolism
  • Animals
  • Blotting, Northern
  • Blotting, Western
  • COS Cells
  • Cell Line, Tumor
  • Chlorocebus aethiops
  • Gene Expression Regulation, Neoplastic
  • HeLa Cells
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms, Experimental / genetics
  • Liver Neoplasms, Experimental / metabolism
  • Liver Neoplasms, Experimental / pathology
  • Lutheran Blood-Group System / genetics*
  • Lutheran Blood-Group System / metabolism
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Oncogene Proteins / genetics*
  • Oncogene Proteins / metabolism
  • Promoter Regions, Genetic / genetics
  • Protein Binding
  • Rats
  • Receptors, Laminin / genetics
  • Receptors, Laminin / metabolism
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription, Genetic / genetics
  • Transplantation, Heterologous

Substances

  • 14-3-3 Proteins
  • BCAM protein, rat
  • Lutheran Blood-Group System
  • Membrane Glycoproteins
  • Oncogene Proteins
  • Receptors, Laminin
  • Repressor Proteins

Grant support

This work was supported by the Ministry of Education, Culture, Sports, Science and Technology Grants-in-Aid for Scientific Research Grant Numbers 70089332, 23701104, 25870775. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.