The pogo transposable element derived zinc finger protein, POGZ, is notably associated with neurodevelopmental disorders through its role in gene transcription. Many proteins involved in neurological development are often dysregulated in cancer, suggesting a potential role for POGZ in tumor biology. Here, we provided experimental evidence that POGZ influences the growth and metastatic spread of triple negative breast cancers (TNBC). In well-characterized models of TNBC, POGZ exerted a dual role, both as a tumor promoter and metastasis suppressor. Mechanistically, loss of POGZ potentiated TGFβ pathway activation to exert cytostatic effects while simultaneously increasing the mesenchymal and migratory properties of breast tumors. Whereas POGZ levels are elevated in human breast cancers, the most aggressive forms of TNBC tumors, including those with increased mesenchymal and metastatic properties, exhibit dampened POGZ levels, and low POGZ expression was associated with inferior clinical outcomes in these tumor types. Taken together, these data suggest that POGZ is a critical suppressor of the early stages of the metastatic cascade.

中文翻译：

---

神经发育蛋白 POGZ 通过减弱 TGFβ 信号传导抑制三阴性乳腺癌的转移


pogo 转座因子衍生的锌指蛋白 POGZ 通过其在基因转录中的作用与神经发育障碍显着相关。许多参与神经发育的蛋白质在癌症中经常失调，这表明 POGZ 在肿瘤生物学中具有潜在作用。在这里，我们提供了实验证据，证明 POGZ 影响三阴性乳腺癌 （TNBC） 的生长和转移扩散。在特征明确的 TNBC 模型中，POGZ 发挥双重作用，既是肿瘤促进剂又是转移抑制剂。从机制上讲，POGZ 的缺失增强了 TGFβ 通路激活以发挥细胞抑制作用，同时增加了乳腺肿瘤的间充质和迁移特性。虽然 POGZ 水平在人乳腺癌中升高，但最具侵袭性的 TNBC 肿瘤形式，包括间充质和转移特性增加的肿瘤，表现出抑制的 POGZ 水平，并且低 POGZ 表达与这些肿瘤类型的不良临床结果相关。综上所述，这些数据表明 POGZ 是转移级联反应早期阶段的关键抑制因子。