Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou 325000, China.
Department of Clinical Laboratory, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325035, China.
Int J Mol Sci. 2022 Oct 19;23(20):12532. doi: 10.3390/ijms232012532.
SOX2, a member of the SRY-related HMG-box (SOX) family, is abnormally expressed in many tumors and associated with cancer stem cell-like properties. Previous reports have shown that SOX2 is a biomarker for cancer stem cells in human bladder cancer (BC), and our most recent study has indicated that the inhibition of SOX2 by anticancer compound ChlA-F attenuates human BC cell invasion. We now investigated the mechanisms through which SOX2 promotes the invasive ability of BC cells. Our studies revealed that SOX2 promoted SKP2 transcription and increased SKP2-accelerated Sp1 protein degradation. As Sp1 is a transcriptionally regulated gene, transcription was thereby attenuated, and, in the absence of HUR, mRNA was degraded fast, which promoted BC cell invasion. In addition, SOX2 promoted BC invasion through the upregulation of nucleolin transcription, which resulted in increased mRNA stability and expression. Collectively, our findings show that SOX2 promotes BC invasion through both SKP2-Sp1-HUR-FOXO1 and nucleolin-MMP2 dual axes.
SOX2 是 SRY 相关 HMG 盒（SOX）家族的成员，在许多肿瘤中异常表达，并与癌症干细胞样特性相关。先前的报告表明，SOX2 是人膀胱癌（BC）中的癌症干细胞标志物，我们最近的研究表明，抗癌化合物 ChlA-F 抑制 SOX2 可减弱人 BC 细胞的侵袭。我们现在研究了 SOX2 促进 BC 细胞侵袭能力的机制。我们的研究表明，SOX2 促进 SKP2 转录并增加 SKP2 加速的 Sp1 蛋白降解。由于 Sp1 是转录调控基因，因此转录受到抑制，并且在没有 HUR 的情况下，mRNA 快速降解，从而促进 BC 细胞侵袭。此外，SOX2 通过核仁素转录的上调促进 BC 侵袭，导致更多的 mRNA 稳定性和表达。总之，我们的研究结果表明，SOX2 通过 SKP2-Sp1-HUR-FOXO1 和核仁素-MMP2 双轴促进 BC 侵袭。
