The FBI1/Akirin2 target gene, BCAM, acts as a suppressive oncogene
Hirotada Akiyama1, Yoshimasa Iwahana, Mikiya Suda
1Department 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.
Insights
Basal cell adhesion molecule (BCAM) acts as a tumor suppressor, inhibiting hepatoma cell growth and metastasis. The oncogenic 14-3-3β-FBI1/Akirin2 complex represses BCAM, promoting cancer progression.
Area of Science:
- Molecular Biology
- Oncology
- Cell Biology
Background:
- Basal cell adhesion molecule (BCAM), a splicing variant of Lutheran glycoprotein (LU), is an immunoglobulin superfamily protein and a laminin α5 receptor.
- BCAM/LU's role in sickle cell disease pathogenesis and development is known, but its function in carcinogenesis is unclear.
- The oncogenic 14-3-3β-FBI1/Akirin2 complex functions as a transcriptional repressor, inhibiting MAPK phosphatase-1 gene expression.
Purpose of the Study:
- To investigate the function of BCAM in malignant tumors, specifically hepatoma.
- To elucidate the mechanism by which the 14-3-3β-FBI1/Akirin2 complex regulates BCAM expression.
- To determine BCAM's role as a potential tumor suppressor or oncogene in hepatoma.
Main Methods:
- Microarray expression analysis to identify BCAM as a target gene of the 14-3-3β-FBI1/Akirin2 complex.
- Establishment of BCAM-expressing hepatoma K2 cells to assess phenotypic changes.
- Luciferase reporter assays and chromatin immunoprecipitation to analyze BCAM promoter activity and protein-DNA interactions.
Main Results:
- BCAM-expressing hepatoma cells exhibited reduced malignant characteristics, including anchorage-independent growth, migration, invasion, and tumorigenicity.
- The 14-3-3β-FBI1/Akirin2 complex was found to bind to the BCAM promoter and repress its transcription.
- These findings identify BCAM as a suppressive oncoprotein and implicate FBI1/Akirin2 in hepatoma tumorigenesis and metastasis via BCAM downregulation.
Conclusions:
- BCAM functions as a tumor suppressor in hepatoma, counteracting malignant phenotypes.
- The oncogenic complex FBI1/Akirin2 contributes to hepatoma progression by downregulating the tumor-suppressive BCAM.
- Targeting the FBI1/Akirin2-BCAM pathway may offer therapeutic strategies for hepatoma treatment.
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