Golgi dispersal in cancer stem cells promotes chemoresistance of colorectal cancer via the Golgi stress response
Abstrak
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.
Topik & Kata Kunci
Penulis (8)
Yangkun Li
Lei Mu
Yanqi Li
Yulong Mi
Yibing Hu
Xiaolan Li
Deding Tao
Jichao Qin
Akses Cepat
- Tahun Terbit
- 2024
- Sumber Database
- DOAJ
- DOI
- 10.1038/s41419-024-06817-0
- Akses
- Open Access ✓