Kuang Junqi, Li Pengli, Zhai Ziwei, Fan Yixin, Xu HuaiYuan, Zhao Chengchen, Li Wei, Li Xiaoxi, Liang Zechuan, Huang Tao, Qin Yue, Gao Huiru, Ma Zhaoyi, Liu Dong, Zhong Guifa, Wang Bo, Liu Jing, Wang Jin, Tortorella Micky D, Liao Baojian, Pei Duanqing
Laboratory of Cell Fate Control, School of Life Sciences, Westlake University, Hangzhou, China.
Institute of Biology, Westlake Institute for Advanced Study, Hangzhou, China.
Mol Cancer. 2024 Apr 27;23(1):85. doi: 10.1186/s12943-024-02002-1.
Nuclear condensates have been shown to regulate cell fate control, but its role in oncogenic transformation remains largely unknown. Here we show acquisition of oncogenic potential by nuclear condensate remodeling. The proto-oncogene SS18 and its oncogenic fusion SS18-SSX1 can both form condensates, but with drastically different properties and impact on 3D genome architecture. The oncogenic condensates, not wild type ones, readily exclude HDAC1 and 2 complexes, thus, allowing aberrant accumulation of H3K27ac on chromatin loci, leading to oncogenic expression of key target genes. These results provide the first case for condensate remodeling as a transforming event to generate oncogene and such condensates can be targeted for therapy. One sentence summary: Expulsion of HDACs complexes leads to oncogenic transformation.
核凝聚物已被证明可调节细胞命运控制,但其在致癌转化中的作用仍 largely 未知。在此我们展示了通过核凝聚物重塑获得致癌潜能。原癌基因 SS18 及其致癌融合体 SS18-SSX1 均可形成凝聚物,但具有截然不同的特性以及对三维基因组结构的影响。致癌凝聚物而非野生型凝聚物容易排除 HDAC1 和 2 复合物,因此,使得 H3K27ac 在染色质位点异常积累,导致关键靶基因的致癌性表达。这些结果为凝聚物重塑作为产生癌基因的转化事件提供了首个实例,并且此类凝聚物可成为治疗靶点。一句话总结:HDACs 复合物的排出导致致癌转化。