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Peer-reviewedCC BY-NC-ND 4.0Communications Biology

Non-canonical role of Ku80 stabilizes Rab7A to enhance mitolysosome formation and chemotherapy in liver cancer

  • Baojia Zou1
  • Lukun Yang1,2
  • Yihua Dai1,2
  • Peiping Li1
  • Manyao Zhang2
  • Bailiang He3
  • Jianzhong He4
  • Decheng Li1
  • En Lin1
  • Chaonong Cai1
  • Yiguang Lin5
  • Mingjian Lu6
1 more authors
  • Jian Li1
6 affiliations
  1. 1Department of Hepatobiliary Surgery, the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China
  2. 2Department of Anesthesiology, the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China
  3. 3Guangdong Provincial Key Laboratory of Biomedical Imaging, Guangdong Provincial Engineering Research Center of Molecular Imaging, the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China
  4. 4Department of Pathology, the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China
  5. 5Department of Oncology, Guangdong Provincial Hospital of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
  6. 6Department of Interventional Radiology, Guangzhou Institute of Cancer Research, the Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou, China
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Abstract

Targeting mitophagy is a potential strategy to tackle chemoresistance and improve chemotherapy in cancer. Ku80 is reported to play a role in chemoresistance and could exert non-canonical functions in mitophagy, but the mechanism remains largely unknown. Here, we report that increased expression of Ku80 leads to prominent mitophagy in liver cancer cells and tissues. Mechanistically, Ku80 directly regulates Rab7A to enhance formation of mitolysosomes. Elevated cytoplasmic levels of Ku80 and Rab7A in liver cancer tissues correlate with improved disease-free survival (DFS) and overall survival (OS) and significantly enhance the efficacy of adjuvant chemotherapy in surgical liver cancer patients. Several FDA-approved drugs can be repurposed as mitophagy activators, which enhance the chemotherapeutic agent epirubicin and Ku80/Rab7A interactions. Therefore, we have discovered the non-canonical role of Ku80 in mitophagy by directly regulating Rab7A in liver cancer, which is a potentially druggable and molecular subtyping strategy to improve chemotherapy outcomes.

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Cite

BibTeXRIS
BibTeX
@article{zou2026noncanonical,
  title = {{Non-canonical role of Ku80 stabilizes Rab7A to enhance mitolysosome formation and chemotherapy in liver cancer}},
  author = {Baojia Zou and Lukun Yang and Yihua Dai and Peiping Li and Manyao Zhang and Bailiang He and Jianzhong He and Decheng Li and En Lin and Chaonong Cai and Yiguang Lin and Mingjian Lu and Jian Li},
  journal = {Communications Biology},
  year = {2026},
  month = jul,
  doi = {10.1038/s42003-026-10554-9},
  url = {https://doi.org/10.1038/s42003-026-10554-9},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Non-canonical role of Ku80 stabilizes Rab7A to enhance mitolysosome formation and chemotherapy in liver cancer
AU  - Baojia Zou
AU  - Lukun Yang
AU  - Yihua Dai
AU  - Peiping Li
AU  - Manyao Zhang
AU  - Bailiang He
AU  - Jianzhong He
AU  - Decheng Li
AU  - En Lin
AU  - Chaonong Cai
AU  - Yiguang Lin
AU  - Mingjian Lu
AU  - Jian Li
PY  - 2026
DA  - 2026/07/03
JO  - Communications Biology
DO  - 10.1038/s42003-026-10554-9
UR  - https://doi.org/10.1038/s42003-026-10554-9
AB  - Targeting mitophagy is a potential strategy to tackle chemoresistance and improve chemotherapy in cancer. Ku80 is reported to play a role in chemoresistance and could exert non-canonical functions in mitophagy, but the mechanism remains largely unknown. Here, we report that increased expression of Ku80 leads to prominent mitophagy in liver cancer cells and tissues. Mechanistically, Ku80 directly regulates Rab7A to enhance formation of mitolysosomes. Elevated cytoplasmic levels of Ku80 and Rab7A in liver cancer tissues correlate with improved disease-free survival (DFS) and overall survival (OS) and significantly enhance the efficacy of adjuvant chemotherapy in surgical liver cancer patients. Several FDA-approved drugs can be repurposed as mitophagy activators, which enhance the chemotherapeutic agent epirubicin and Ku80/Rab7A interactions. Therefore, we have discovered the non-canonical role of Ku80 in mitophagy by directly regulating Rab7A in liver cancer, which is a potentially druggable and molecular subtyping strategy to improve chemotherapy outcomes.
SN  - 2399-3642
ER  -