2. Academic Validation
  3. Golgi dispersal in cancer stem cells promotes chemoresistance of colorectal cancer via the Golgi stress response

Golgi dispersal in cancer stem cells promotes chemoresistance of colorectal cancer via the Golgi stress response

  • Cell Death Dis. 2024 Jun 15;15(6):417. doi: 10.1038/s41419-024-06817-0.
Yangkun Li 1 2,  Lei Mu 1 2,  Yanqi Li 1 2,  Yulong Mi 1 3,  Yibing Hu 1 4,  Xiaolan Li 1,  Deding Tao 1,  Jichao Qin 5 6 7
Affiliations

Affiliations

  • 1 Molecular Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.
  • 2 Department of Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.
  • 3 Department of Surgical Oncology, Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, 350013, Fujian, China.
  • 4 Department of Breast Surgery, Peking University Shenzhen Hospital, Shenzhen, 518000, Guangdong, China.
  • 5 Molecular Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China. jcqin@tjh.tjmu.edu.cn.
  • 6 Department of Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China. jcqin@tjh.tjmu.edu.cn.
  • 7 Department of Gastrointestinal Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, Zhejiang, China. jcqin@tjh.tjmu.edu.cn.
PMID: 38879509 DOI: 10.1038/s41419-024-06817-0
Abstract

Chemotherapy is a crucial treatment for colorectal tumors. However, its efficacy is restricted by chemoresistance. Recently, Golgi dispersal has been suggested to be a potential response to chemotherapy, particularly to drugs that induce DNA damage. However, the underlying mechanisms by which Golgi dispersal enhances the capacity to resist DNA-damaging agents remain unclear. Here, we demonstrated that DNA-damaging agents triggered Golgi dispersal in colorectal Cancer (CRC), and Cancer Stem Cells (CSCs) possessed a greater degree of Golgi dispersal compared with differentiated Cancer cells (non-CSCs). We further revealed that Golgi dispersal conferred resistance against the lethal effects of DNA-damaging agents. Momentously, Golgi dispersal activated the Golgi stress response via the PKCα/GSK3α/TFE3 axis, resulting in enhanced protein and vesicle trafficking, which facilitated drug efflux through ABCG2. Identification of Golgi dispersal indicated an unexpected pathway regulating chemoresistance in CRC.

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