FUNDC2, a mitochondrial outer membrane protein, mediates triple-negative breast cancer progression via the AKT/GSK3β/GLI1 pathway

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Triple-negative breast cancer (TNBC) presents significant therapeutic challenges due to a lack of targeted treatments and a tendency for recurrence and metastasis.
• Identifying novel therapeutic targets is crucial for improving TNBC patient prognosis.

Purpose of the Study:

• To identify and validate novel therapeutic targets for triple-negative breast cancer.
• To investigate the functional role and underlying mechanism of the outer mitochondrial membrane protein FUNDC2 in TNBC progression.

Main Methods:

• Mass spectrometry and qRT-PCR validation were employed to identify potential targets.
• High-content screening and analysis of clinical breast cancer samples were performed.
• In vitro studies involved gene silencing in TNBC cells, assessing proliferation, migration, and invasion.
• In vivo studies utilized subcutaneous tumor xenografts in mice to evaluate tumor growth inhibition.

Main Results:

• FUNDC2 expression was significantly elevated in TNBC tissues compared to luminal subtype breast cancer tissues.
• Silencing FUNDC2 in TNBC cells markedly reduced cell proliferation, migration, and invasion.
• In vivo, suppression of FUNDC2 significantly inhibited tumor growth in mouse xenograft models.
• Mechanistically, FUNDC2 inactivation affected the AKT/GSK3β and Hedgehog signaling pathways (GLI1).

Conclusions:

• FUNDC2 is upregulated in TNBC and promotes tumor progression.
• FUNDC2 plays a critical role in TNBC cell proliferation, migration, and invasion.
• FUNDC2 represents a potential therapeutic target for the treatment of triple-negative breast cancer.