TP53基因突变在食管鳞状细胞癌（ESCC）和其他鳞状细胞癌中较为频繁，并且与转移的倾向有关。在这里，我们报告，巢细胞刺激因子-1（Csf-1）在ESCC的肺转移病灶中以p53-R172H依赖性显著上调表达。p53-R172H依赖的Csf-1信号通过其相应的受体Csf-1r增加了肿瘤细胞的侵袭性和肺转移，其中一部分通过Stat3磷酸化和上皮-间质转化介导。在Trp53R172H肿瘤细胞中，p53占据了Csf-1启动子区域。Csf-1基因位点富集了组蛋白3赖氨酸27乙酰化（H3K27ac），这可能有助于促进Brd4和p53-R172H之间的相互作用以调控Csf-1的转录。抑制Brd4不仅可以减少肿瘤侵袭和肺转移，而且可以降低循环中的Csf-1水平。总的来说，我们的结果建立了一个新的p53-R172H依赖性Brd4-Csf-1轴，促进了ESCC的肺转移，并为这种难以治疗的疾病的治疗策略提供了思路。

TP53 mutations are frequent in esophageal squamous cell carcinoma (ESCC) and other SCCs, and are associated with a proclivity for metastasis. Here, we report that Colony-stimulating factor-1 (Csf-1) expression is upregulated significantly in a p53-R172H-dependent manner in metastatic lung lesions of ESCC. The p53-R172H-dependent Csf-1 signaling through its cognate receptor Csf-1r increases tumor cell invasion and lung metastasis, which in turn is mediated in part through Stat3 phosphorylation and epithelial-to-mesenchymal transition. In Trp53R172H tumor cells, p53 occupies the Csf-1 promoter. The Csf-1 locus is enriched with histone 3 lysine 27 acetylation (H3K27ac), which likely is permissive for fostering an interaction between Brd4 and p53-R172H to regulate Csf-1 transcription. Inhibition of Brd4 not only reduces tumor invasion and lung metastasis, but also reduces circulating Csf-1 levels. Overall, our results establish a novel p53-R172H-dependent Brd4-Csf-1 axis that promotes ESCC lung metastasis, and suggest avenues for therapeutic strategies for this difficult-to-treat disease.