2. Academic Validation
  3. Acetylation suppresses breast cancer progression by sustaining CLYBL stability

Acetylation suppresses breast cancer progression by sustaining CLYBL stability

  • J Transl Med. 2025 Apr 10;23(1):415. doi: 10.1186/s12967-025-06200-3.
Xinyue Deng # 1 2,  Chenglong Ma # 3,  Xingyu Chen 4,  Ming Yi 5,  Qianhua Cao 4,  Ruocen Liao 3,  Xingyu Lei 2,  Longchang Bai 3,  Bin Zhao 5,  Yingnan Wang 5,  Zhuoyang Shen 5,  Liujing Wu 1 2,  Chenfang Dong 6,  Zhijun Dai 7
Affiliations

Affiliations

  • 1 Otolaryngology & Head and Neck Center, Cancer Center, Department of Head and Neck Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China.
  • 2 Zhejiang Provincial Clinical Research Center for Malignant Tumor, Hangzhou, 310014, China.
  • 3 Zhejiang Key Laboratory for Disease Proteomics, Zhejiang University School of Medicine, Hangzhou, 310058, China.
  • 4 Department of Respiratory and Critical Care Medicine, Key Laboratory of Respiratory Disease of Ningbo, The First Affiliated Hospital of Ningbo University, Ningbo, China.
  • 5 Department of Breast Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China.
  • 6 Zhejiang Key Laboratory for Disease Proteomics, Zhejiang University School of Medicine, Hangzhou, 310058, China. chenfangdong@zju.edu.cn.
  • 7 Department of Breast Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China. dzj0911@zju.edu.cn.
  • # Contributed equally.
PMID: 40211376 DOI: 10.1186/s12967-025-06200-3
Abstract

Background: The incidence of breast Cancer remains high and it remains the leading cause of cancer-related deaths in women. A better understanding of the molecular mechanisms of breast Cancer and identifying novel biomarkers will help improve therapeutic strategies. Citrate lyase beta like (CLYBL) is expressed at low levels in breast Cancer tissues and is associated with low patient survival rates. In this study, we explored the regulatory mechanisms of CLYBL and its acetylation in breast Cancer.

Methods: CLYBL expression patterns in breast Cancer were assessed using a breast Cancer tissue microarray, immunohistochemistry, and publicly available datasets. The acetylation patterns of CLYBL and the related regulatory functions were detected by high resolution mass spectrometry, immunoprecipitation assays, and western blot analysis. The potential effects of CLYBL and its acetylation on breast Cancer were determined using both in vitro and in vivo assays.

Results: CLYBL was expressed at lower levels in breast Cancer samples compared with normal tissues. This low CLYBL expression was associated with poor patient survival rates. Overexpressing CLYBL could inhibit breast Cancer and reduce NRF2 pathway-mediated Antioxidants. We identified two acetylated lysine sites in CLYBL, K57 and K82, using acetylated peptide affinity enrichment and high-resolution mass spectrometry. Our results suggest that K82 is the main acetylation site. Further work showed that the p300/CBP associated factor (PCAF) and histone deacetylase 3 (HDAC3) as the CLYBL acetyltransferase and deacetylase, respectively. Additionally, CLYBL acetylation facilitates its own protein stability by reducing it affinity for ubiquitin, thus enhancing the anti-breast Cancer effects.

Conclusion: We revealed the role of CLYBL overexpression and its acetylation in breast Cancer. Our study suggests that CLYBL is a potential molecular target for breast Cancer therapy.

Keywords

Acetylation; Breast cancer (BC); CLYBL; HDAC3; PCAF.

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