本文采用的英格恩产品: 其它病毒感染增强试剂
UBAP2L-driven stress granule formation links oxaliplatin resistance to gastric cancer
Affiliations
- 1 Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
- 2 Department of Immunology, Shenzhen Majory Biotechnology Co. Ltd., Shenzhen, China.
- 3 Department of Anesthesiology, The Third Xiangya Hospital, Central South University, Changsha, China.
- 4 Departments of Colorectal Surgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.
- 5 Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China. gzlianzy@163.com.
- 6 Department of Burn and Plastic Surgery, Southern Theater General Hospital, Guangzhou, China.
- 7 Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
- 8 Department of breast surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.
- 9 Zhanjiang Key Laboratory of Intelligent Diagnosis and Treatment of Breast Cancer, Zhanjiang, China.
- 10 Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Clinical Research Academy of Chinese Medicine, Guangzhou, China.
- 11 Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China. gzliguoxin@163.com.
- 12 Cancer Center of Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua Medicine, Tsinghua University, Beijing, China. gzliguoxin@163.com.
- PMID: 40804300
- PMCID: PMC12350937
- DOI: 10.1038/s42003-025-08584-w
Abstract
Stress granules (SGs), which are phase-separating organelles that serve as protective cellular mechanisms in response to various harmful stimuli, have an unclear role in oxaliplatin resistance. Here, we establish a causal link between SG formation and oxaliplatin resistance in GC. Notably, we identify a key SG nucleator, namely, ubiquitin-associated protein 2-like (UBAP2L), as a previously unrecognized critical factor in mediating oxaliplatin resistance. UBAP2L-nucleated SG-mediated inhibition of apoptosis is associated with the recruitment of receptor of activated protein C kinase 1 (RACK1), a known promoter of apoptosis, to these entities. Transcriptional upregulation of UBAP2L is enhanced by oxaliplatin-induced phosphorylation and activation of heat shock factor protein 1 (HSF1) via AKT. Inhibiting either SG or HSF1 significantly overcomes oxaliplatin resistance in vivo. These findings demonstrate that UBAP2L-nucleated SGs play a vital role in mediating oxaliplatin resistance, with elevated SG levels emerging as a promising therapeutic target for overcoming this resistance.
