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Peer-reviewedCC BY-NC-ND 4.0NPJ Precision Oncology

DCAF13: a positive regulator of colon cancer cell proliferation via the AMER2/ Wnt/β-catenin pathway

  • Yu-Xin Hua1,2
  • Jie Gao1,3
  • Qing-Qing Sun1,4
  • Xiao-Min Wang1
  • Jing-Yu Wang5
  • Yuan Zhou6
  • Long Zhang7
  • Xian-Chao Zhang8
  • Chun-Wei Xu9
  • Bing Bao10
  • Su-Ping Tao11
  • Ying Xu1
3 more authors
  • Wei-Wei Pan1,12,13
  • Shu-Qun Cheng14
  • Sheng-Bing Liu1
14 affiliations
  1. 1Department of Histoembryology and Cell Biology, College of Medicine, Jiaxing University, Jiaxing, China
  2. 2Zhejiang Chinese Medicine University and Jiaxing University Master Degree Cultivation Base, Jiaxing University, Jiaxing, China
  3. 3Department of Geriatrics, Ulanqab City Center Hospital, Ulanqab City, China
  4. 4College of Pharmacy, Zhejiang University of Technology, Hangzhou, China
  5. 5Department of Pathology, First Affiliated Hospital of Jiaxing University/The First Hospital of Jiaxing, Jiaxing, China
  6. 6Department of Gastrointestinal Surgery, First Affiliated of Jiaxing University/ The First Hospital of Jiaxing, Jiaxing, China
  7. 7Department of Anesthesiology, Baoji People’s Hospital, Baoji, China
  8. 8Institute of Information Network and Artificial Intelligence, Jiaxing University, Jiaxing, China
  9. 9Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China
  10. 10Department of Gastrointestinal Surgery, Tongcheng People’s Hospital, Tongcheng, China
  11. 11Gynecology department, First Affiliated Hospital of Jiaxing University/The First Hospital of Jiaxing, Jiaxing, China
  12. 12G60 STI Valley Industry & Innovation Institute, Jiaxing University, Jiaxing, China
  13. 13Engineering Research Center of Intelligent Human Health Situation Awareness of Zhejiang Province, Jiaxing University, Jiaxing, China
  14. 14Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
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Abstract

The Wnt/β-catenin pathway plays a critical role in colorectal cancer (CRC) development. The significance of Wnt/β-catenin in maintaining the stability of adult tissues and challenges in identifying suitable molecular targets have limited the application of targeting the Wnt/β-catenin pathway. As one of the Cullin RING Ligase 4 adapters, DNA damage-binding protein 1 (DDB1) - and CUL4 correlation factor 13 (DCAF13) appears strongly expressed in different tumors. Our findings confirm enhanced expression of DCAF13 in tissues of CRC origin and related cell. In colon cancer cells, DCAF13 regulated adenomatous polyposis coli membrane recruitment 2 (AMER2) through ubiquitination, DCAF13 deletion increased AMER2 expression, which inhibited Wnt/β-catenin activity, suppressing cell proliferation. This effect was further validated in mice with gut-specific DCAF13 knockout. The ubiquitin-proteasome system is a potential target for drug development and cancer treatment. Beta-propeller proteins, such as CRL4 adapter DCAFs, are easily targeted by drugs. DCAF-proteolysis-targeting chimeras (PROTACs) can overcome drug resistance and selectively target tumor drivers by leveraging the unique substrate specificity of the DCAF subunits. DCAF13 emerges as a promising target for CRC, acting via the DCAF13-AMER2-Wnt /β-catenin axis.

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Cite

BibTeXRIS
BibTeX
@article{hua2026dcaf13,
  title = {{DCAF13: a positive regulator of colon cancer cell proliferation via the AMER2/ Wnt/β-catenin pathway}},
  author = {Yu-Xin Hua and Jie Gao and Qing-Qing Sun and Xiao-Min Wang and Jing-Yu Wang and Yuan Zhou and Long Zhang and Xian-Chao Zhang and Chun-Wei Xu and Bing Bao and Su-Ping Tao and Ying Xu and Wei-Wei Pan and Shu-Qun Cheng and Sheng-Bing Liu},
  journal = {NPJ Precision Oncology},
  year = {2026},
  month = jul,
  doi = {10.1038/s41698-026-01603-x},
  url = {https://doi.org/10.1038/s41698-026-01603-x},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - DCAF13: a positive regulator of colon cancer cell proliferation via the AMER2/ Wnt/β-catenin pathway
AU  - Yu-Xin Hua
AU  - Jie Gao
AU  - Qing-Qing Sun
AU  - Xiao-Min Wang
AU  - Jing-Yu Wang
AU  - Yuan Zhou
AU  - Long Zhang
AU  - Xian-Chao Zhang
AU  - Chun-Wei Xu
AU  - Bing Bao
AU  - Su-Ping Tao
AU  - Ying Xu
AU  - Wei-Wei Pan
AU  - Shu-Qun Cheng
AU  - Sheng-Bing Liu
PY  - 2026
DA  - 2026/07/13
JO  - NPJ Precision Oncology
DO  - 10.1038/s41698-026-01603-x
UR  - https://doi.org/10.1038/s41698-026-01603-x
AB  - The Wnt/β-catenin pathway plays a critical role in colorectal cancer (CRC) development. The significance of Wnt/β-catenin in maintaining the stability of adult tissues and challenges in identifying suitable molecular targets have limited the application of targeting the Wnt/β-catenin pathway. As one of the Cullin RING Ligase 4 adapters, DNA damage-binding protein 1 (DDB1) - and CUL4 correlation factor 13 (DCAF13) appears strongly expressed in different tumors. Our findings confirm enhanced expression of DCAF13 in tissues of CRC origin and related cell. In colon cancer cells, DCAF13 regulated adenomatous polyposis coli membrane recruitment 2 (AMER2) through ubiquitination, DCAF13 deletion increased AMER2 expression, which inhibited Wnt/β-catenin activity, suppressing cell proliferation. This effect was further validated in mice with gut-specific DCAF13 knockout. The ubiquitin-proteasome system is a potential target for drug development and cancer treatment. Beta-propeller proteins, such as CRL4 adapter DCAFs, are easily targeted by drugs. DCAF-proteolysis-targeting chimeras (PROTACs) can overcome drug resistance and selectively target tumor drivers by leveraging the unique substrate specificity of the DCAF subunits. DCAF13 emerges as a promising target for CRC, acting via the DCAF13-AMER2-Wnt /β-catenin axis.
SN  - 2397-768X
ER  -