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.

Plos One
|November 14, 2013
PubMed

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.

Related Concept Videos

The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.2K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
7.1K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.6K
Induced Pluripotent Stem Cells01:06

Induced Pluripotent Stem Cells

Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic...
4.8K
Immunoglobulin-like Cell Adhesion Molecules01:31

Immunoglobulin-like Cell Adhesion Molecules

Immunoglobulin-like cell adhesion molecules or Ig-CAMs are a versatile group of cell surface glycoproteins belonging to the immunoglobulin protein superfamily. Ig-CAMs possess the characteristic immunoglobulin protein domains and other domains such as the fibronectin type III domain. The Ig domains are glycosylated to varying degrees in different Ig-CAMs.
Ig-CAMs exhibit either homophilic binding (to other Ig-CAMs) or heterophilic binding (to other ligands such as integrins). While most Ig-CAMs...
3.3K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
7.3K