2. Academic Validation
  3. Exclusion of HDAC1/2 complexes by oncogenic nuclear condensates

Exclusion of HDAC1/2 complexes by oncogenic nuclear condensates

  • Mol Cancer. 2024 Apr 27;23(1):85. doi: 10.1186/s12943-024-02002-1.
Junqi Kuang # 1 2 3,  Pengli Li # 4 5 6,  Ziwei Zhai # 4 5 6,  Yixin Fan # 4 5 6,  HuaiYuan Xu # 7,  Chengchen Zhao 1,  Wei Li 4 5 6,  Xiaoxi Li 4 5 6,  Zechuan Liang 1 2,  Tao Huang 1 2,  Yue Qin 1 2,  Huiru Gao 4 5 6,  Zhaoyi Ma 1 2,  Dong Liu 1 2,  Guifa Zhong 8,  Bo Wang 1 2,  Jing Liu 4 5,  Jin Wang 9,  Micky D Tortorella 10,  Baojian Liao 11 12 13 14,  Duanqing Pei 15 16
Affiliations

Affiliations

  • 1 Laboratory of Cell Fate Control, School of Life Sciences, Westlake University, Hangzhou, China.
  • 2 Institute of Biology, Westlake Institute for Advanced Study, Hangzhou, China.
  • 3 Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, 310024, Zhejiang, China.
  • 4 CAS Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
  • 5 Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
  • 6 University of Chinese Academy of Sciences, Beijing, China.
  • 7 Department of Musculoskeletal Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China.
  • 8 Centre for Regenerative Medicine and Health, Hong Kong Institute of Science and Innovation, Chinese Academy of Sciences 5/F, 15 Science Park West Ave., Hong Kong Science Park, Park Shek Kok, New Territories, Hong Kong SAR, China.
  • 9 Department of Musculoskeletal Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China. wangjinr@sysucc.org.cn.
  • 10 Centre for Regenerative Medicine and Health, Hong Kong Institute of Science and Innovation, Chinese Academy of Sciences 5/F, 15 Science Park West Ave., Hong Kong Science Park, Park Shek Kok, New Territories, Hong Kong SAR, China. m.tortorella@gibh.ac.cn.
  • 11 CAS Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China. liaobaojian@gzhmu.edu.cn.
  • 12 Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China. liaobaojian@gzhmu.edu.cn.
  • 13 Laboratory of Stem Cell and Regenerative Biology, the Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan, China. liaobaojian@gzhmu.edu.cn.
  • 14 Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. liaobaojian@gzhmu.edu.cn.
  • 15 Laboratory of Cell Fate Control, School of Life Sciences, Westlake University, Hangzhou, China. peiduanqing@westlake.edu.cn.
  • 16 Institute of Biology, Westlake Institute for Advanced Study, Hangzhou, China. peiduanqing@westlake.edu.cn.
  • # Contributed equally.
PMID: 38678233 DOI: 10.1186/s12943-024-02002-1
Abstract

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.

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