前列腺癌干细胞（PCSC）在去势抵抗性前列腺癌（CRPC）的治疗抵抗和转移中发挥着至关重要的作用。 CRPC 涉及癌症干性和上皮间质转化 (EMT) 之间的某些功能联系。然而，人们对 PCSC 中控制这两个过程的上游监管机构仍然知之甚少。最近，我们发现孤儿核受体TLX可以通过抑制雄激素受体和癌基因诱导的衰老来促进CRPC中肿瘤的发生和进展。通过多种体外和体内方法从多种前列腺癌细胞系和临床肿瘤组织中分离PCSCs。体内致癌生长分析。通过特异性报告基因测定和配体驱动的 TLX 活性调节，确定了 TLX 参与干性和 EMT 调节的直接靶标。从各种来源分离的 PCSC 表现出 TLX 表达增加。功能和分子表征表明，TLX 可以通过直接反式激活 CD44、SOX2、POU5F1 和 NANOG 来促进前列腺癌细胞的癌症干细胞性和 EMT，这两个细胞过程在这两个细胞过程中具有一定的功能串扰。TLX 可以作为关键- PCSC 干性和 EMT 转录控制中的流调节器，这有助于晚期前列腺癌的致瘤性、去势抵抗和转移潜力。© 2024。作者，获得 Springer Nature Limited 的独家许可。

Prostate cancer stem cells (PCSCs) play crucial roles in therapy-resistance and metastasis in castration-resistant prostate cancer (CRPC). Certain functional link between cancer stemness and epithelial-mesenchymal transition (EMT) is involved in CRPC. However, up-stream regulators controlling these two processes in PCSCs are still poorly understood. Recently, we have shown that orphan nuclear receptor TLX can promote tumour initiation and progression in CRPC by repressing androgen receptor and oncogene-induced senescence.PCSCs were isolated from various prostate cancer cell lines and clinical tumour tissues using multiple methods for various in vitro and in vivo oncogenic growth analyses. Direct targets of TLX involved in stemness and EMT regulation were determined by specific reporter gene assays and ligand-driven modulation of TLX activity.PCSCs isolated from various sources exhibited increased expression of TLX. Functional and molecular characterisation showed that TLX could function to promote cancer stemness and EMT in prostate cancer cells via its direct transactivation of CD44, SOX2, POU5F1 and NANOG, which share certain functional crosstalk in these two cellular processes.TLX could act as a key up-stream regulator in transcriptional control of stemness and EMT in PCSCs, which contribute to their tumorigenicity, castration-resistance and metastasis potentials in advanced prostate cancer.© 2024. The Author(s), under exclusive licence to Springer Nature Limited.