FAM83D promotes cell proliferation and motility by downregulating tumor suppressor gene FBXW7

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Amplification of chromosome 20q is a common event in human cancers, including breast cancer.
• The 20q amplicon contains several candidate oncogenes implicated in tumorigenesis.
• The role of Family with sequence similarity 83, member D (FAM83D) in breast cancer remains largely unexplored.

Purpose of the Study:

• To investigate the role of FAM83D in breast cancer development and progression.
• To determine the clinical significance and prognostic value of FAM83D expression in breast cancer patients.

Main Methods:

• Analysis of FAM83D expression in breast cancer cell lines and primary tumors.
• Correlation of FAM83D expression with clinical outcomes and patient metastasis.
• Functional studies involving ectopic expression and ablation of FAM83D in mammary epithelial and breast cancer cells.
• Mechanistic investigations into FAM83D's interaction with FBXW7 and its downstream targets like mTOR.

Main Results:

• FAM83D expression is significantly elevated in breast cancer cell lines and primary tumors.
• High FAM83D levels correlate with poor clinical outcome and increased distant metastasis.
• Ectopic FAM83D expression promotes proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT).
• FAM83D ablation induces apoptosis and inhibits proliferation and colony formation.
• FAM83D physically interacts with FBXW7, downregulating its expression and leading to mTOR hyper-activation.
• Inhibition of mTOR by rapamycin suppresses FAM83D-induced migration and invasion.

Conclusions:

• FAM83D is a novel oncogene in breast cancer development.
• FAM83D possesses significant prognostic value for breast cancer patients.
• FAM83D promotes breast cancer progression, at least partly through mTOR hyper-activation via FBXW7 inhibition.