Objective:

To investigate the role of RSPO2 in breast cancer progression and its relationship with ferroptosis.

Key Findings:

• RSPO2 is downregulated in malignant breast cancer tissues.
• Restoring RSPO2 expression suppresses cell proliferation, migration, and invasion in vitro and inhibits tumor growth in vivo.
• RSPO2 recruits TRIM21 to promote PTBP1 ubiquitination and degradation.
• PTBP1 stabilizes FSP1 mRNA; RSPO2 overexpression reduces PTBP1 levels, leading to decreased FSP1 mRNA stability.
• RSPO2 overexpression triggers ferroptosis, evidenced by ROS accumulation and GSH depletion.

Interpretation:

RSPO2 acts as a tumor suppressor in breast cancer by degrading PTBP1, which in turn reduces FSP1 mRNA stability and promotes ferroptosis.

Limitations:

• The study primarily focuses on in vitro and xenograft models, which may not fully replicate human breast cancer complexity.

Conclusion:

The RSPO2/PTBP1/FSP1 signaling axis is identified as a novel therapeutic target in breast cancer.