SERPINE1 promotes CRC cell invasion and metastasis through resistance to anoikis.

Colorectal cancer (CRC) is one of the most common and lethal malignancies worldwide, and its tumor ecosystem remains highly complex and incompletely understood. Here, we analyzed 3,264 single-cell transcriptomes from primary CRC tumors obtained from nine patients in the GSE110009 dataset. We identified 15 distinct cell clusters corresponding to seven major cell types. Trajectory inference (pseudotime analysis) was performed to characterize lineage relationships and cellular developmental trajectories. Genes associated with distinct expression programs were classified into two clusters exhibiting different tumor microenvironment (TME) characteristics. Functional enrichment analysis revealed that epithelial-mesenchymal transition (EMT) plays a critical role in CRC tumorigenesis and metastasis. Moreover, we established a novel three-gene prognostic signature that effectively predicts clinical outcomes in CRC patients. Further analyses revealed that SERPINE1 promotes CRC cell invasion and metastasis by enhancing resistance to anoikis. Furthermore, SERPINE1 was found to enhance the malignant phenotype of metastatic colorectal cancer cells. Collectively, these findings reveal the immunosuppressive landscape of the CRC TME, provide new insights into CRC progression, and identify SERPINE1 as a potential prognostic biomarker and therapeutic target.