DCAF13 promotes ovarian cancer progression by activating FRAS1-mediated FAK signaling pathway
Cullin-RING ubiquitin ligase 4 (CRL4) is closely correlated with the incidence and progression of ovarian cancer. DDB1- and CUL4-associated factor 13 (DCAF13), a substrate-recognition protein in the CRL4 E3 ubiquitin ligase complex, is involved in the occurrence and development of ovarian cancer. However, its precise function and the underlying molecular mechanism in this disease remain unclear. In this study, we confirmed that DCAF13 is highly expressed in human ovarian cancer and its expression is negatively correlated with the overall survival rate of patients with ovarian cancer. We then used CRISPR/Cas9 to knockout DCAF13 and found that its deletion significantly inhibited the proliferation, colony formation, and migration of human ovarian cancer cells. In addition, DCAF13 deficiency inhibited tumor proliferation in nude mice. Mechanistically, CRL4-DCAF13 targeted Fraser extracellular matrix complex subunit 1 (FRAS1) for polyubiquitination and proteasomal degradation. FRAS1 influenced the proliferation and migration of ovarian cancer cell through induction of the focal adhesion kinase (FAK) signaling pathway. These findings collectively show that DCAF13 is an important oncogene that promotes tumorigenesis in ovarian cancer cells by mediating FRAS1/FAK signaling. Our findings provide a foundation for the development of targeted therapeutics for ovarian cancer.
Authors
- Weiwei Pan (ORCID: https://orcid.org/0000-0002-3574-3758)
- Ze-Yi Tang
- Xiaomin Wang (ORCID: https://orcid.org/0000-0001-7128-8097)
- Xuan Che (ORCID: https://orcid.org/0000-0002-7514-4100)
- Zha‐Jun Zhan (ORCID: https://orcid.org/0000-0001-7865-5435)
- Shengbing Liu
- Yu-Xin Hua (ORCID: https://orcid.org/0009-0001-0545-5763)
- Qiyin Zhou (ORCID: https://orcid.org/0000-0003-3603-8214)
- Han-Yin Hu
- Michal Heger (ORCID: https://orcid.org/0000-0002-0630-4465)
- Qian Wang (ORCID: https://orcid.org/0000-0002-1346-9524)
- Aijun Liu (ORCID: https://orcid.org/0000-0001-7103-138X)
- Xin Zheng (ORCID: https://orcid.org/0000-0002-4153-8515)
- Shuqun Cheng (ORCID: https://orcid.org/0000-0002-6098-8028)
- Yanjun Guo (ORCID: https://orcid.org/0000-0003-1832-1921)
- Xianchao Zhang (ORCID: https://orcid.org/0000-0001-8925-8371)
- Lei Ao
- C. Xu (ORCID: https://orcid.org/0000-0002-9021-6731)
- Qing-Qing Sun
Institutions
- Ministry of Education (NZ)
- Nanjing University of Chinese Medicine (CN)
- Second Military Medical University (CN)
- Utrecht University (NL)
- Chinese Academy of Sciences (CN)
- XinHua Hospital (CN)
- Chinese PLA General Hospital (CN)
- Jiaxing University (CN)
- Eastern Hepatobiliary Surgery Hospital (CN)
- First Hospital of Jiaxing (CN)
- Zhejiang University of Technology (CN)
- Erasmus University Rotterdam (NL)
Publication Details
- Journal
- Cellular and Molecular Life Sciences
- Published
- 2024-10-05
- DOI
- https://doi.org/10.1007/s00018-024-05446-2
- Citations
- 3
- Primary Topic
- Cell Adhesion Molecules Research
- Type
- article
- Field-Weighted Citation Impact
- 1.15
Funders
- National Natural Science Foundation of China
- Natural Science Foundation of Zhejiang Province