SERPINE1 drives molecular synergies in colorectal cancer

Colorectal cancer is a complex disease shaped by genetic changes and cross talk among tumor cells, stromal factors, and infiltrating cellular elements within the tumor environment. In this review, we explore an integrative network of genes and their encoded proteins that play significant roles in colorectal cancer progression. Among the most clinically relevant and frequently implicated factors in digestive system cancer is the prominent protumorigenic serine protease inhibitor SERPINE1 (also known as plasminogen activator inhibitor-1 or PAI-1). This SERPIN impacts critical pathways that regulate extracellular matrix remodeling, neoplastic and immune cell migration, tumor cell survival, metastasis, and drug resistance, and plays a major role in shaping the neoplastic inflammatory microenvironment. As a result of this multifaceted function, PAI-1 correlates with high-risk scores and poor patient outcomes in various malignancies including colorectal cancer. Recent bioinformatic approaches provide new insights on how PAI-1 contributes to tumor progression and patient prognosis. This review provides a unified framework for understanding this disease at the molecular level and highlights promising targets for future therapies and diagnosis.