The AU-rich element RNA-binding protein 1 (AUF1) is an RNA-binding protein, which can both stabilize and destabilize the transcripts of several cancer-related genes. Since epithelial-to-mesenchymal transition (EMT) and the acquisition of cancer stem cell traits are important for cancer onset and progression, we sought to determine the role of AUF1 in these two important processes. We have shown that AUF1 induces EMT and stemness in breast epithelial cells via stabilization of the SNAIL1 and TWIST1 mRNAs, and their consequent upregulation. Indeed, AUF1 binds the transcripts of these two genes at their 3′UTR and reduces their turnover. Ectopic expression of AUF1 also promoted stemness in mammary epithelial cells, and thereby increased the proportion of cancer stem cells. Importantly, breast cancer cells that ectopically express AUF1 were more efficient in forming orthotopic tumor xenografts in nude mice than their corresponding controls with limiting cell inocula. On the other hand, AUF1 downregulation with specific siRNA inhibited EMT and reduced the stemness features in breast cancer cells. Moreover, AUF1 knockdown sensitized breast cancer cells to the killing effect of cisplatin. Together, these findings provide clear evidence that AUF1 is an important inducer of the EMT process through stabilization of SNAIL1 and TWIST1 and the consequent promotion of breast cancer stem cells. Thereby, AUF1 targeted molecules could constitute efficient therapeutics for breast cancer patients.

富含AU的元素RNA结合蛋白1（AUF1）是一种RNA结合蛋白，可以稳定和破坏几种癌症相关基因的转录本。由于上皮到间质转化（EMT）和癌症干细胞性状的获得对于癌症的发作和进展很重要，因此我们试图确定AUF1在这两个重要过程中的作用。我们已经表明，AUF1通过稳定SNAIL1和TWIST1诱导乳腺上皮细胞EMT和干性mRNA及其随后的上调。实际上，AUF1在其3'UTR处结合了这两个基因的转录本，并减少了其周转率。AUF1的异位表达还促进了乳腺上皮细胞的干性，从而增加了癌症干细胞的比例。重要的是，异位表达AUF1的乳腺癌细胞在裸鼠体内形成原位肿瘤异种移植物的效率要高于其相应的带有有限细胞接种量的对照。另一方面，使用特定siRNA的AUF1下调抑制了EMT并降低了乳腺癌细胞的干性特征。而且，AUF1敲低可使乳腺癌细胞对顺铂的杀伤作用敏感。在一起，这些发现提供了明确的证据，即AUF1通过SNAIL1的稳定化是EMT过程的重要诱因。与TWIST1和随之而来的促进乳腺癌干细胞的。因此，AUF1靶向分子可以构成乳腺癌患者的有效疗法。