2. Academic Validation
  3. NSCLC cells sustain phase separation of cytoplasmic membrane-less organelles to protect themselves against cisplatin treatment

NSCLC cells sustain phase separation of cytoplasmic membrane-less organelles to protect themselves against cisplatin treatment

  • Acta Pharmacol Sin. 2025 Apr 17. doi: 10.1038/s41401-025-01551-5.
Ning-Ning Li # 1,  Ling-Ling Rao # 1,  Dan Su # 1,  Bin-Hao Liu # 1,  Guo-Qiang Ma 1,  Hong-Feng Wang 2 3,  Zeng-Li Zhang 4,  Zheng Ying 5 6 7
Affiliations

Affiliations

  • 1 Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, China.
  • 2 Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, China. wanghongfeng@suda.edu.cn.
  • 3 MOE Key Laboratory of Geriatric Diseases and Immunology, College of Pharmaceutical Sciences, Suzhou Medical College of Soochow University, Suzhou, 215004, China. wanghongfeng@suda.edu.cn.
  • 4 Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Soochow University, Suzhou, 215123, China. zenglizhang@126.com.
  • 5 Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, China. zheng.ying@suda.edu.cn.
  • 6 MOE Key Laboratory of Geriatric Diseases and Immunology, College of Pharmaceutical Sciences, Suzhou Medical College of Soochow University, Suzhou, 215004, China. zheng.ying@suda.edu.cn.
  • 7 Jiangsu Province Engineering Research Center of Precision Diagnostics and Therapeutics Development, Soochow University, Suzhou, 215123, China. zheng.ying@suda.edu.cn.
  • # Contributed equally.
PMID: 40247038 DOI: 10.1038/s41401-025-01551-5
Abstract

Cisplatin is the first platinum compound used for Anticancer therapy, including non-small cell lung Cancer (NSCLC). However, the clinical efficacy of cisplatin is strongly limited by cisplatin resistance. Hence, illuminating the mechanism of cisplatin resistance will aid in the development of therapeutic strategies that improve the sensitivity of Cancer cells to cisplatin. Interestingly, membrane-less organelles, which are formed through biomolecular condensation in association with phase separation, have been recently linked with cancers. Here, we reveal a new molecular basis of cisplatin resistance in NSCLC, showing that cisplatin kills Cancer cells by the alteration of cytoplasmic membrane-less organelles. Specifically, cisplatin treatment results in the disassembly of processing bodies (PBs) and the assembly of stress granule (SG)-like granules which are different from canonical SGs in NSCLC cells, but not cisplatin-resistant NSCLC cells. Moreover, alterations of PBs and noncanonical SG-like granules are associated with cisplatin-induced Cancer cell death. Importantly, we found that disrupting PBs and canonical SGs with cycloheximide and FDA-approved pyrvinium helps cisplatin to kill cisplatin-resistant NSCLC cells. Taken together, our findings provide insight into the role of membrane-less organelle regulation in cisplatin resistance and offer an effective solution for overcoming cisplatin resistance in NSCLC.

Keywords

cisplatin resistance; membrane-less organelle; phase separation; processing body; stress granule-like granule.

Figures
Products