SERPINE1: Role in Cholangiocarcinoma Progression and a Therapeutic Target in the Desmoplastic Microenvironment

Abstract

A heterogenous population of inflammatory elements, other immune and nonimmune cells and cancer-associated fibroblasts (CAFs) are evident in solid malignancies where they coexist with the growing tumor mass. In highly desmoplastic malignancies, CAFs are the prominent mesenchymal cell type in the tumor microenvironment (TME), where their presence and abundance signal a poor prognosis. CAFs play a major role in the progression of various cancers by remodeling the supporting stroma into a dense, fibrotic matrix while secreting factors that promote the maintenance of cancer stem-like characteristics, tumor cell survival, aggressive growth and metastasis and reduced sensitivity to chemotherapeutics. Tumors with high stromal fibrotic signatures are more likely to be associated with drug resistance and eventual relapse. Identifying the molecular underpinnings for such multidirectional crosstalk among the various normal and neoplastic cell types in the TME may provide new targets and novel opportunities for therapeutic intervention. This review highlights recent concepts regarding the complexity of CAF biology in cholangiocarcinoma, a highly desmoplastic cancer. The discussion focuses on CAF heterogeneity, functionality in drug resistance, contributions to a progressively fibrotic tumor stroma, the involved signaling pathways and the participating genes.

Identification of adipocyte infiltration-related gene subtypes for predicting colorectal cancer prognosis and responses of immunotherapy/chemotherapy

“…ADIPOQ (adiponectin) is an adipokine with anti-inflammatory and insulin-sensitizing properties, and its reduced expression is associated with cancer progression [ 25 ]. SERPINE1 (plasminogen activator inhibitor-1) regulates fibrinolysis and extracellular matrix degradation, promoting tumor invasion and metastasis [ 26 ]. These core genes collectively contribute to the tumor microenvironment, influencing processes such as angiogenesis, extracellular matrix remodeling, lipid metabolism, and immune response, thereby playing a critical role in tumor invasion and progression.…”