NSD1 promotes esophageal cancer tumorigenesis via HIF1α signaling

Unlike angiogenesis in normal tissues, tumor angiogenesis is typically dysregulated, during which the HIF1/VEGFA signaling pathway plays a pivotal role. Solid tumors generate immature vessels, which promote tumor progression and treatment resistance. NSD1 can di-methylate histone 3 lysine 36 and regulate transcription factors binding to the promoters of various genes. However, the role of NSD1 in tumorigenesis remains elusive. Here, we evaluated the relationship between NSD1 signaling and HIF1 signaling. It was found that NSD1 transcriptionally regulates HIF1 alpha expression by recruiting STAT3 molecule into the HIF1 alpha promoter. In vivo xenograft experiments further confirmed that HIF1 alpha and STAT3 maintenance is essential for NSD1-mediated tumor progression and angiogenesis. Therefore, the NSD1/STAT3/HIF1 alpha signaling pathway may be a novel and effective treatment target for ESCA.