Effects of SLC2A1 knockdown in intrahepatic cholangiocarcinoma (ICC) cancer-associated fibroblasts (CAFs) on endothelial sprouting under normal and hypoxic conditions
Hypoxia is a critical determinant of endothelial sprouting. We here demonstrate that hypoxia-driven remodeling of the ICC tumor microenvironment promotes the emergence of a distinct CAF subset, termed tumor-like CAF (tCAF). We further identify SLC2A1 in tCAFs as a potential key regulator that facilitates endothelial sprouting, although the underlying molecular mechanisms remain to be elucidated. Collectively, our data provide a molecular basis for the aggressive vascular invasive phenotype of ICC and delineate a hypoxia–tCAF–endothelial cell signaling axis, highlighting SLC2A1 as a potential therapeutic target for disrupting tumor angiogenesis in ICC. Overall design: RNA sequencing analysis of wild-type ICC CAF cells and their shSLC2A1 knockdown cells under normal and hypoxic conditions.