与正常组织中的血管生成不同，肿瘤血管生成通常是失调的，其中HIF1 / VEGFA信号通路发挥着关键作用。实体肿瘤产生不成熟的血管，促进肿瘤进展和治疗抵抗力。NSD1可以双甲基化组蛋白3赖氨酸36并调节转录因子结合各种基因的启动子。然而，NSD1在肿瘤发生中的作用仍不清楚。在这里，我们评估了NSD1信号与HIF1信号之间的关系。发现NSD1通过招募STAT3分子到HIF1α启动子中对HIF1α的表达进行转录调控。体内异种移植实验进一步证实了HIF1α和STAT3的维持对于NSD1介导的肿瘤进展和血管生成是必要的。因此，NSD1 / STAT3 / HIF1α信号通路可能是ESCA的一种新的和有效的治疗靶点。©2022。作者（们），在Springer Nature B.V.的独家许可下。

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 HIF1α expression by recruiting STAT3 molecule into the HIF1α promoter. In vivo xenograft experiments further confirmed that HIF1α and STAT3 maintenance is essential for NSD1-mediated tumor progression and angiogenesis. Therefore, the NSD1/STAT3/HIF1α signaling pathway may be a novel and effective treatment target for ESCA.© 2022. The Author(s), under exclusive licence to Springer Nature B.V.