Department of Urology, Shengjing Hospital of China Medical University, Shenyang 110001, Liaoning, China.
Department of Pathology, Shengjing Hospital of China Medical University, Shenyang 110001, Liaoning, China.
Biochem Pharmacol. 2023 Dec;218:115893. doi: 10.1016/j.bcp.2023.115893. Epub 2023 Oct 27.
Prostate cancer (PCa) remains the most common malignant tumor in men, and the clinical treatment still faces many challenges. Several molecular biomarkers of PCa progression have been reported, however, whether FOXS1 can serve as a new biomarker in PCa remains unknown.
FOXS1 and Gli1 expression was assessed by RT-qPCR and western blot. The binding and regulation roles between FOXS1 and Gli1 were confirmed by Co-IP and ubiquitination assays. Cell viability, proliferation, apoptosis, migration, invasion and EMT progress were assessed through CCK-8, colony formation, flow cytometry, wound-healing, transwell and western blot assays, respectively. In vivo nude mice tumorigenesis model was also conducted to verify PCa growth.
FOXS1 was upregulated in the PCa TCGA dataset and cells. High FOXS1 level was correlated with PCa patients' worse tumor stage and shorter survival. FOXS1 knockdown inhibited PCa cell proliferation, invasion, migration, EMT and tumor growth while increased cell apoptosis. Furthermore, FOXS1 knockdown decreased the inactivation of Hedgehog (Hh) pathway. FOXS1 bind to Gli1 and decreased the ubiquitination of Gli1, which resulted in the upregulation of Gli1. Besides, both Gil1 overexpression and Hh signal activation reversed the suppression function of FOXS1 silencing on PCa growth and metastasis.
FOXS1 bind and stabilized Gli1 by blocking Gli1 ubiquitination, thereby activating Hh signaling to promote PCa cell growth and metastasis.
前列腺癌（PCa）仍然是男性最常见的恶性肿瘤，临床治疗仍然面临许多挑战。已经报道了几种 PCa 进展的分子生物标志物，然而，FOXS1 是否可以作为 PCa 的新生物标志物尚不清楚。
通过 RT-qPCR 和 Western blot 评估 FOXS1 和 Gli1 的表达。通过 Co-IP 和泛素化测定证实 FOXS1 和 Gli1 之间的结合和调节作用。通过 CCK-8、集落形成、流式细胞术、划痕愈合、Transwell 和 Western blot 测定分别评估细胞活力、增殖、凋亡、迁移、侵袭和 EMT 进展。还进行了体内裸鼠肿瘤发生模型以验证 PCa 生长。
FOXS1 在 PCa TCGA 数据集和细胞中上调。高水平的 FOXS1 与 PCa 患者更差的肿瘤分期和更短的生存时间相关。FOXS1 敲低抑制了 PCa 细胞的增殖、侵袭、迁移、EMT 和肿瘤生长，同时增加了细胞凋亡。此外，FOXS1 敲低降低了 Hedgehog (Hh) 通路的失活。FOXS1 与 Gli1 结合并减少 Gli1 的泛素化，从而导致 Gli1 的上调。此外，Gli1 过表达和 Hh 信号激活均逆转了 FOXS1 沉默对 PCa 生长和转移的抑制作用。
FOXS1 通过阻断 Gli1 泛素化来结合和稳定 Gli1，从而激活 Hh 信号通路促进 PCa 细胞的生长和转移。
