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
  • 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. [email protected].
  • 6. Department of Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China. [email protected].
  • 7. Department of Gastrointestinal Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, Zhejiang, China. [email protected].
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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