TAF7 directly targets SAA1 to enhance triple-negative breast cancer metastasis via phosphorylating E-cadherin and N-cadherin
Identification of metastasis drivers of triple-negative breast cancer (TNBC) is a multifaceted challenge. Here, we identified TATA-box binding protein associated factor 7 (TAF7) as a candidate to modulate TNBC metastasis. TAF7 exhibited high expression in metastatic TNBC patients, and its elevated expression showed a negative correlation with overall survival in TNBC patients. The knockdown of TAF7 suppressed the migration and invasion of TNBC, suggesting TAF7 plays a role in the metastatic processes. Further, TAF7 was enhancing serum amyloid A1 (SAA1) transcription by binding to a specific motif in the SAA1 gene promoter. The elevated SAA1 in TNBC cells directly increased E-cadherin and N-cadherin phosphorylation thereby regulating cell adhesion. Mechanistically, TAF7 modulated cell invasion, migration, and lung metastasis through an SAA1-dependent manner <i>in vitro</i> and <i>in vivo</i> experiments. Taken together, it is likely that TAF7 could directly act on the SAA1 gene promoter, upregulating SAA1 and consequently promoting TNBC metastasis.
Authors
- Haichuan Zhu (ORCID: https://orcid.org/0000-0002-4232-835X)
- Tong Lai
- Jiaqi Nie
- Xinhong Zhou
- Hanning Li (ORCID: https://orcid.org/0000-0001-6281-6994)
- Dao‐Xin Yao (ORCID: https://orcid.org/0000-0003-1097-3802)
- Yoshimasa Tanaka (ORCID: https://orcid.org/0000-0002-5024-0614)
- Huimin Zhang (ORCID: https://orcid.org/0000-0002-5359-1399)
- Xue Zhang (ORCID: https://orcid.org/0000-0002-0914-7872)
- Wanjun Zhang (ORCID: https://orcid.org/0000-0003-2725-3182)
- Xingrui Li (ORCID: https://orcid.org/0000-0002-6572-7740)
- Yiping Gong
- Lin Su (ORCID: https://orcid.org/0000-0002-3389-2063)
- Jun Wang (ORCID: https://orcid.org/0009-0008-8475-2934)
- Xinghua Liao
Institutions
- Kyoto University (JP)
- Wuhan University (CN)
- Renmin Hospital of Wuhan University (CN)
- Tongji Hospital (CN)
- Wuhan University of Science and Technology (CN)
- Huazhong University of Science and Technology (CN)
Publication Details
- Journal
- iScience
- Published
- 2025-02-10
- DOI
- https://doi.org/10.1016/j.isci.2025.111989
- Citations
- 1
- Primary Topic
- Cancer-related gene regulation
- Type
- article
- Field-Weighted Citation Impact
- 0.81
Funders
- National Natural Science Foundation of China
- Ministry of Science and Technology of the People's Republic of China
- Huazhong University of Science and Technology
- Natural Science Foundation of Hubei Province
- International Science and Technology Cooperation Programme