Hyperactivation of EGFR and downstream effector phospholipase D1 by oncogenic FAM83B

R Cipriano1, B L Bryson1, K L S Miskimen1

  • 1Department of Pathology, Case Western Reserve University, Cleveland, OH, USA.

Oncogene
|August 6, 2013
PubMed

Insights

Researchers identified FAM83B as a novel oncogene that drives cancer by increasing Phospholipase D (PLD) activity and interacting with the epidermal growth factor receptor (EGFR). Targeting this interaction may offer new cancer therapy strategies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Targeted anticancer therapies are advancing, yet new therapeutic targets are crucial for expanding treatment options.
  • FAM83B has been identified as a potential oncogene involved in human mammary epithelial cell transformation.

Purpose of the Study:

  • To elucidate the mechanism by which FAM83B contributes to cancer development.
  • To investigate the role of FAM83B in regulating Phospholipase D (PLD) activity and its interaction with the epidermal growth factor receptor (EGFR).

Main Methods:

  • Investigated the effect of FAM83B expression on PLD activity in human mammary epithelial cells.
  • Examined the interaction between FAM83B and EGFR using site-directed mutagenesis.
  • Assessed the impact of FAM83B ablation on EGFR phosphorylation, MAPK signaling, and cell proliferation in breast cancer cells.

Main Results:

  • Elevated FAM83B expression increases PLD activity, which is essential for FAM83B-mediated cell transformation.
  • FAM83B interacts with EGFR, and this interaction is critical for engaging PLD activity.
  • Preventing the FAM83B/EGFR interaction suppresses PLD activity, MAPK signaling, and cell proliferation.
  • Ablation of FAM83B inhibits EGFR phosphorylation and reduces breast cancer cell growth.

Conclusions:

  • FAM83B acts as an oncogene by mediating the interaction between EGFR and PLD, thereby activating downstream signaling pathways.
  • Understanding the FAM83B-EGFR-PLD axis provides a basis for developing novel cancer therapies targeting this pathway.
  • FAM83B represents a promising therapeutic target for cancers driven by EGFR signaling.

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