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

Hirotada Akiyama; Yoshimasa Iwahana; Mikiya Suda; Atsunori Yoshimura; Hiroyuki Kogai; Ai Nagashima; Hiroko Ohtsuka; Yuko Komiya; Fumio Tashiro

doi:10.1371/journal.pone.0078716

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.

Authors

Hirotada Akiyama¹, Yoshimasa Iwahana, Mikiya Suda, Atsunori Yoshimura, Hiroyuki Kogai, Ai Nagashima, Hiroko Ohtsuka, Yuko Komiya, Fumio Tashiro

Affiliation

¹ Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science, Katsushika-ku, Tokyo, Japan.

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

Grants and funding

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.