2. Academic Validation
  3. P300-dependent acetylation of the FOXQ1 complex activates super-enhancers to promote colorectal cancer proliferation and metastasis

P300-dependent acetylation of the FOXQ1 complex activates super-enhancers to promote colorectal cancer proliferation and metastasis

  • Commun Biol. 2025 Jul 7;8(1):1016. doi: 10.1038/s42003-025-08430-z.
Wen-Dong Yang # 1,  Zhi-Heng Zhang # 1,  Man-Yi Zhao # 2,  Ke Shao # 3,  Yan-Feng Ma 4,  Qi Shen 1,  Meng-Ru Lu 1,  Zhi-Ying Shao 1,  Jia-Yu Xu 2,  Meng-Han Cao 5,  Seng Meng 1,  Su-Fang Chu 1,  Hong-Mei Yong 6,  Jin Ding 7,  Jin Bai 8 9 10
Affiliations

Affiliations

  • 1 Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China.
  • 2 Department of Oncology, The Affiliated Huai'an Hospital of Xuzhou Medical University and The Second People's Hospital of Huai'an, Huai'an, Jiangsu, China.
  • 3 Hepatobiliary Center, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
  • 4 Cardiology Department, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
  • 5 Center of Clinical Oncology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
  • 6 Department of Oncology, The Affiliated Huai'an Hospital of Xuzhou Medical University and The Second People's Hospital of Huai'an, Huai'an, Jiangsu, China. Ha2280@126.com.
  • 7 Department of Gastroenterology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang, China. jhDingJin@zju.edu.cn.
  • 8 Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China. bj@xzhmu.edu.cn.
  • 9 Cardiology Department, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China. bj@xzhmu.edu.cn.
  • 10 Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China. bj@xzhmu.edu.cn.
  • # Contributed equally.
PMID: 40624346 DOI: 10.1038/s42003-025-08430-z
Abstract

The FOX transcription factor family plays a pivotal role in the malignant progression of tumors. We propose a hypothesis that FOXQ1 recruits p300 and BRD4 to super-enhancer regions. Our findings indicate that p300 acetylates Lys190 of FOXQ1, resulting in its recognition and binding by BRD4. Subsequently, BRD4 recruits RNA-Pol II to form a "FOXQ1-p300-BRD4-RNA Pol II" complex, which then binds to the super-enhancers of target genes. Meanwhile, acetylation at Lys190 of FOXQ1 directly enhances its binding affinity to super-enhancers. Consequently, more target oncogenes can be transcribed to promote CRC proliferation and metastasis. Our results suggest that FOXQ1 acts as a key regulator of super-enhancers, providing insights into its role in CRC and highlighting its potential as a therapeutic target.

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