Kurosu Haruka, Yamada Norika, Nakamura Ritsuko, Ito Hideaki, Ohnishi Koji, Inoko Akihito, Riku Miho, Muramatsu Tomoaki, Sassa Naoto, Kasai Kenji
Department of Urology, Aichi Medical University School of Medicine, Japan.
Department of Pathology, Aichi Medical University School of Medicine, Japan.
Biochem Biophys Rep. 2025 Jun 20;43:102101. doi: 10.1016/j.bbrep.2025.102101. eCollection 2025 Sep.
The facilitates chromatin transcription (FACT) complex is composed of SSRP1 and SUPT16H subunits and participates in nucleosomal reorganization; hence, FACT inhibitors are considered promising therapeutics for malignant tumors. Here, we show that adipocyte enhancer binding protein 1 (AEBP1) attenuates the dependency of bladder cancer cell survival on the FACT complex the expression of GLI1, a pivotal transcription factor in Hedgehog signaling. In -high expressing bladder cancer cell lines, knockdown inhibited cellular proliferation and induced the marker expression of apoptosis and DNA damage/replication stress. RNA-sequencing revealed that knockdown suppressed the expression of and ; however, the knockdown of both subunits was less effective than knockdown in inducing apoptosis or DNA damage markers in -high expressing cells. knockdown reduced the protein levels of GLI1, and treatment with the GLI-specific inhibitor GANT61 induced markers that were not suppressed by the forced expression of AEBP1. These findings suggest that AEBP1-mediated GLI1 expression reduces the FACT complex dependency of bladder cancer cell survival.
促进染色质转录（FACT）复合物由SSRP1和SUPT16H亚基组成，并参与核小体重组；因此，FACT抑制剂被认为是恶性肿瘤的有前景的治疗药物。在此，我们表明脂肪细胞增强子结合蛋白1（AEBP1）减弱了膀胱癌细胞存活对FACT复合物的依赖性，FACT复合物是刺猬信号通路中关键转录因子GLI1的表达所必需的。在GLI1高表达的膀胱癌细胞系中，AEBP1敲低抑制细胞增殖并诱导凋亡和DNA损伤/复制应激的标志物表达。RNA测序显示，AEBP1敲低抑制了GLI1和SUFU的表达；然而，在GLI1高表达细胞中，两个亚基的敲低在诱导凋亡或DNA损伤标志物方面不如AEBP1敲低有效。AEBP1敲低降低了GLI1的蛋白水平，并且用GLI特异性抑制剂GANT61处理诱导了未被AEBP1强制表达所抑制的标志物。这些发现表明，AEBP1介导的GLI1表达降低了膀胱癌细胞存活对FACT复合物的依赖性。
