Coiled-coil domain containing 3 suppresses breast cancer growth by protecting p53 from proteasome-mediated...

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Coiled-coil domain containing 3 (CCDC3) was known for regulating liver lipid metabolism.
• Its role in cancer, particularly breast cancer, was previously unexplored.

Purpose of the Study:

• To investigate the potential role of CCDC3 as a tumor suppressor in breast cancer.
• To elucidate the underlying molecular mechanisms of CCDC3's function in breast cancer.

Main Methods:

• Bioinformatic analysis of CCDC3 expression in breast cancer datasets.
• In vitro studies involving ectopic CCDC3 expression and CRISPR-Cas9 mediated depletion.
• Xenograft tumor models in mice.
• Co-immunoprecipitation assays to study protein-protein interactions.

Main Results:

• CCDC3 is significantly under-expressed in breast cancers and correlates with poorer patient survival.
• Overexpression of CCDC3 suppresses breast cancer cell proliferation, colony formation, and tumor growth by enhancing p53 activity.
• CCDC3 depletion increases proliferation and drug resistance by reducing p53 activity.
• CCDC3 stabilizes nuclear p53 by binding to p53 and MDM2, preventing p53 degradation.
• A positive feedback loop exists where p53 induces CCDC3 expression.

Conclusions:

• CCDC3 functions as an intracellular tumor suppressor in breast cancer.
• CCDC3 stabilizes p53, inhibiting breast cancer progression through a novel feedback mechanism.
• CCDC3 represents a potential therapeutic target for breast cancer treatment.