SP1 drives colorectal cancer progression via transcriptional activation of SERPINE1

Background Colorectal cancer (CRC) remains a leading cause of cancer-related mortality, with tumor microenvironment (TME) remodeling playing a key role in disease progression and therapy resistance. Serine protease inhibitor clade E member 1 (SERPINE1) is implicated in TME modulation and poor prognosis, but its upstream regulatory mechanism in CRC remains incompletely understood. Results SERPINE1 was identified as a core gene and found to be upregulated in CRC. Silencing SERPINE1 inhibited CRC cell proliferation, invasion, migration, and tumor growth, while its overexpression had the opposite effect. In vitro , SERPINE1 expression correlated with elevated PD-L1 expression and enhanced CD8 + T cell apoptosis of co-cultured CD8 + T cells. Mechanistically, SP1 was upregulated in CRC and was found to bind to the SERPINE1 promoter in vitro . Finally, SP1 exerted part of its pro-tumorigenic and immune-related effects through regulating SERPINE1 in cellular assays. Conclusions SP1 promotes colorectal cancer progression via transcriptional activation of SERPINE1, and its upregulation of SERPINE1 correlates with PD-L1 expression in vitro . How to cite: Fan Y, Liu B, Liu F, et al. SP1 drives colorectal cancer progression via transcriptional activation of SERPINE1. Electron J Biotechnol 2026;84. https://doi.org/10.1016/j.ejbt.2026.100729 .