TRAF2 is an NF-κB-activating oncogene in epithelial cancers.

Area of Science:

• Oncology
• Molecular Biology
• Cancer Genetics

Background:

• Aberrant nuclear factor (NF)-κB activation is a hallmark of human cancers.
• Genetic alterations in NF-κB pathway components are crucial for cancer initiation and progression.

Purpose of the Study:

• To identify novel oncogenes within the NF-κB pathway.
• To investigate the role of tumor necrosis factor (TNF) receptor-associated factor 2 (TRAF2) in human epithelial cancers.

Main Methods:

• Analysis of patient tumors and cancer cell lines for genetic alterations.
• Assessment of TRAF2 copy number gain and rearrangements.
• Functional studies involving TRAF2 suppression and phosphorylation analysis.

Main Results:

• TRAF2 was identified as an oncogene recurrently amplified and rearranged in 15% of human epithelial cancers.
• Suppression of TRAF2 inhibited cancer cell proliferation, NF-κB activation, anchorage-independent growth, and tumorigenesis.
• Cancer cell survival was dependent on both TRAF2 and NF-κB.
• Phosphorylation of TRAF2 at serine 11 was essential for the survival of TRAF2-amplified cancer cells.

Conclusions:

• TRAF2 is a frequently amplified oncogene in human epithelial cancers.
• TRAF2 plays a critical role in cancer cell proliferation, survival, and tumorigenesis.
• Targeting TRAF2 may represent a therapeutic strategy for cancers with TRAF2 amplification.