SERPINE1 Facilitates Metastasis in Gastric Cancer Through Anoikis Resistance and Tumor Microenvironment Remodeling

Area of Science:

• Oncology
• Cancer Biology
• Immunology

Background:

• SERPINE1 (serine protease inhibitor) is upregulated in malignancies, particularly gastric cancer (GC).
• SERPINE1 plays a key role in GC metastasis and shaping the tumor microenvironment (TME).

Purpose of the Study:

• To elucidate the mechanisms of SERPINE1 in mediating anoikis resistance and fostering an immunosuppressive TME in advanced GC.
• To evaluate SERPINE1 as a therapeutic target and predictive biomarker for GC immunotherapy.

Main Methods:

• Analysis of SERPINE1 expression in GC tissues and metastatic lesions.
• Investigating SERPINE1 transcriptional activation by CEBPB and downstream signaling pathways (PI3K/AKT, EMT).
• Examining SERPINE1's role in M2 macrophage polarization and CD8+ T-cell suppression via LRP1 interaction.
• Assessing synergistic effects of SERPINE1 inhibition combined with PD-1 blockade.
• Correlating SERPINE1 expression with recurrence risk after immune checkpoint inhibitor therapy.

Main Results:

• High SERPINE1 expression is linked to poor prognosis and increased metastatic potential in GC.
• SERPINE1 activation of PI3K/AKT and EMT pathways enhances anoikis resistance via autocrine signaling.
• SERPINE1 promotes M2 macrophage polarization and suppresses CD8+ T-cell activity through paracrine LRP1 signaling.
• Combined SERPINE1 inhibition and PD-1 blockade show synergistic antitumor effects.
• Elevated SERPINE1 predicts higher recurrence risk in advanced GC patients treated with immunotherapy.

Conclusions:

• SERPINE1 is a critical driver of GC progression by promoting anoikis resistance and remodeling the TME.
• SERPINE1 represents a promising therapeutic target for advanced GC.
• SERPINE1 serves as a valuable predictive biomarker for immunotherapy response in GC.