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Updated: May 9, 2026

Knockdown of FAM83A to Verify Its Role in Cervical Cancer Cell Growth and Cisplatin Sensitivity
Published on: February 9, 2024
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.
Abstract:
Despite the progress made in targeted anticancer therapies in recent years, challenges remain. The identification of new potential targets will ensure that the arsenal of cancer therapies continues to expand. FAM83B was recently discovered in a forward genetic screen for novel oncogenes that drive human mammary epithelial cell (HMEC) transformation. We report here that elevated FAM83B expression increases Phospholipase D (PLD) activity, and that suppression of PLD1 activity prevents FAM83B-mediated transformation. The increased PLD activity is engaged by hyperactivation of epidermal growth factor receptor (EGFR), which is regulated by an interaction involving FAM83B and EGFR. Preventing the FAM83B/EGFR interaction by site-directed mutation of lysine 230 of FAM83B suppressed PLD activity and MAPK signaling. Furthermore, ablation of FAM83B expression from breast cancer cells inhibited EGFR phosphorylation and suppressed cell proliferation. We propose that understanding the mechanism of FAM83B-mediated transformation will provide a foundation for future therapies aimed at targeting its function as an intermediary in EGFR, MAPK and mTOR activation.
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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