SLC45A4 expression in cancer-associated fibroblasts is associated with epithelial ovarian cancer progression and HIF-1α-glycolysis signaling activation

Cancer-associated fibroblasts (CAFs) play a crucial role in the tumor microenvironment (TME), particularly in promoting the malignant progression of tumors. Although the role of CAFs is widely acknowledged, their specific regulatory mechanisms in the progression of epithelial ovarian cancer (EOC) remain to be elucidated. This study used conditioned medium from primary EOC-associated CAFs (CAF-CM) to culture EOC cell lines, revealing the critical role of CAFs in enhancing EOC cell proliferation, migration, and invasion. Bioinformatic analysis of public databases, supported by immunohistochemical staining, identified that SLC45A4—a member of the solute carrier family—is differentially expressed in EOC cells and CAFs, with significant implications in CAFs. In vitro experiments confirmed that CAF-expressed SLC45A4 is associated with the malignant phenotype of EOC cells, potentially through the hypoxia-inducible factor (HIF-1α)-mediated glycolysis signaling pathway, which is closely associated with poor patient prognosis. Moreover, the reduction of SLC45A4 expression in CAFs through gene knockdown technology markedly inhibited tumor growth in mice, offering a novel strategy for TME-based EOC treatment. This study not only provides new insights into the mechanisms of CAFs action in EOC progression but also identifies a potential molecular target for the development of TME-based therapeutic strategies for EOC.