The FBI1/Akirin2 target gene, BCAM, acts as a suppressive oncogene.
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.
Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science, Katsushika-ku, Tokyo, Japan.
Hirotada
H
Akiyama
Yoshimasa
Y
Iwahana
Mikiya
M
Suda
Atsunori
A
Yoshimura
Hiroyuki
H
Kogai
Ai
A
Nagashima
Hiroko
H
Ohtsuka
Yuko
Y
Komiya
Fumio
F
Tashiro
D048948:14-3-3 Proteins / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D019556:COS Cells; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008188:Lutheran Blood-Group System / Q000235:genetics* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D015513:Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D051381:Rats; D017474:Receptors, Laminin / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000235:genetics; D014183:Transplantation, Heterologous
D048948:14-3-3 Proteins; C000590911:BCAM protein, rat; D008188:Lutheran Blood-Group System; D008562:Membrane Glycoproteins; D015513:Oncogene Proteins; D017474:Receptors, Laminin; D012097:Repressor Proteins