2. Academic Validation
  3. β-Hydroxybutyrate promotes cancer metastasis through β-hydroxybutyrylation-dependent stabilization of Snail

β-Hydroxybutyrate promotes cancer metastasis through β-hydroxybutyrylation-dependent stabilization of Snail

  • Nat Commun. 2025 Jul 17;16(1):6592. doi: 10.1038/s41467-025-61541-3.
Wenna Jiang # 1,  Meng Wang # 1 2,  Jiayi Wang # 1,  Qianhui Hao 1,  Yuxuan Li 1,  Lin Liu 1,  Tianxing Zhou 3,  Wei Song 4,  Jing Liu 5 6,  Miao Liu 7,  Yongjie Xie 3,  Duo Zuo 1,  Jiawei Xiao 1,  Xiuse Zhang 1,  Shan Gao 8,  Li Ren 9,  Jihui Hao 10
Affiliations

Affiliations

  • 1 Department of Clinical Laboratory, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Key Laboratory of Digestive Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, China.
  • 2 Department of Clinical Laboratory, The Second Hospital of Tianjin Medical University, Tianjin, China.
  • 3 Department of Pancreatic Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Digestive Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, China.
  • 4 State Key Laboratory of Agricultural and Forestry Biosecurity, College of Plant Protection, Nanjing Agricultural University, Nanjing, China.
  • 5 Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University, Shanghai Cancer Center, Shanghai, China.
  • 6 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
  • 7 Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Immunology and Biotherapy, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, China.
  • 8 Zhongda Hospital, School of Life Sciences and Technology, Advanced Institute for Life and Health, Southeast University, Nanjing, China. gaos@sibet.ac.cn.
  • 9 Department of Clinical Laboratory, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Key Laboratory of Digestive Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, China. liren@tmu.edu.cn.
  • 10 Department of Pancreatic Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Digestive Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, China. haojihui@tjmuch.com.
  • # Contributed equally.
PMID: 40675949 DOI: 10.1038/s41467-025-61541-3
Abstract

β-Hydroxybutyrylation (Kbhb) modification regulates protein molecular fates in either physiology or pathology, including Cancer. However, the function and regulatory mechanism of Kbhb remain completely unknown in Cancer metastasis. Here, we report that β-hydroxybutyrate (BHB) is clinically associated with the progression of pancreatic Cancer and functionally promotes pancreatic Cancer cell metastasis. Mechanistically, BHB induces Kbhb modification of Snail at lysine 152 to enhance Snail stabilization, which is regulated by Kbhb modification enzyme CREB-binding protein (CBP), and subsequently prevents Snail degradation by blocking recognition of E3 ubiquitin ligases FBXL14. Furthermore, either targeting Snail Kbhb modification or CBP inhibitor decreases Cancer metastasis and enhances the therapeutic efficacy of gemcitabine in pancreatic Cancer cells. Collectively, our study reveals that Kbhb of Snail is critical to promote metastasis and provides a potential therapeutic strategy.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z