上皮间质转化 (EMT) 会触发胚胎发育、成人受损组织和癌症中的细胞可塑性。结合对细胞系、胚胎神经嵴以及肾纤维化和乳腺癌小鼠模型中EMT的分析，我们发现不存在针对癌症的EMT方案。相反，在激活胚胎样或成体样 EMT 后，癌细胞会去分化并分叉成两种不同且分离的细胞轨迹，分别驱动扩散或炎症。我们表明，SNAIL1 在两种 EMT 轨迹中均充当先驱因子，而 PRRX1 则驱动胚胎样侵袭轨迹的进展。我们还发现这两条轨迹是可塑的且相互依赖的，因为通过删除 Prrx1 来消除 EMT 侵袭轨迹不仅可以防止转移，还可以增强炎症，增加抗肿瘤巨噬细胞的募集。我们的数据揭示了 EMT 在协调肿瘤内异质性、驱动与炎症或转移性传播相关的功能分布方面的额外作用。© 2024。作者。

Epithelial-to-mesenchymal transition (EMT) triggers cell plasticity in embryonic development, adult injured tissues and cancer. Combining the analysis of EMT in cell lines, embryonic neural crest and mouse models of renal fibrosis and breast cancer, we find that there is not a cancer-specific EMT program. Instead, cancer cells dedifferentiate and bifurcate into two distinct and segregated cellular trajectories after activating either embryonic-like or adult-like EMTs to drive dissemination or inflammation, respectively. We show that SNAIL1 acts as a pioneer factor in both EMT trajectories, and PRRX1 drives the progression of the embryonic-like invasive trajectory. We also find that the two trajectories are plastic and interdependent, as the abrogation of the EMT invasive trajectory by deleting Prrx1 not only prevents metastasis but also enhances inflammation, increasing the recruitment of antitumor macrophages. Our data unveil an additional role for EMT in orchestrating intratumor heterogeneity, driving the distribution of functions associated with either inflammation or metastatic dissemination.© 2024. The Author(s).