2. Academic Validation
  3. STBD1 mediates the crosstalk between glycogen and lipid droplets in clear cell renal cell carcinoma

STBD1 mediates the crosstalk between glycogen and lipid droplets in clear cell renal cell carcinoma

  • Cell Rep. 2025 Oct 28;44(10):116429. doi: 10.1016/j.celrep.2025.116429.
Hao Wang 1,  Tong Xiao 1,  Hao Zhuang 1,  Yi Liu 2,  Kexing Jin 2,  Jing Li 1,  Jun Li 1,  Yan Gao 2,  Dan Yue 3,  Wei Cui 4,  Qingxia Xu 1,  Jingxuan Pan 5,  Kangdong Liu 6,  Yong Wang 7,  Ruibing Chen 8,  Hongle Li 9
Affiliations

Affiliations

  • 1 The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou 450008, China.
  • 2 School of Pharmaceutical Science and Technology, Faculty of Medicine, Tianjin University, Tianjin 300072, China.
  • 3 Department of Microbiology, School of Medical Laboratory, Tianjin Medical University, Tianjin 300203, China.
  • 4 The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou 450008, China; Department of Clinical Laboratory, State Key Laboratory of Molecular Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
  • 5 State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.
  • 6 Department of Pathophysiology, School of Basic Medical Sciences, College of Medicine, Zhengzhou University, Zhengzhou 450001, China; China-US (Henan) Hormel Cancer Institute, Zhengzhou 450008, China.
  • 7 Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin 300211, China. Electronic address: wy@tmu.edu.cn.
  • 8 School of Pharmaceutical Science and Technology, Faculty of Medicine, Tianjin University, Tianjin 300072, China. Electronic address: rbchen@tju.edu.cn.
  • 9 The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou 450008, China; Henan Province Academy of Medical Sciences, Zhengzhou 451162, China. Electronic address: llhl73@163.com.
PMID: 41105508 DOI: 10.1016/j.celrep.2025.116429
Abstract

The accumulation of lipid droplets (LDs) and glycogen is a major hallmark of clear cell renal cell carcinoma (ccRCC), yet their interplay remains unclear. By proteomic profiling of 50 ccRCC tumors, we observe activation of glycogen- and LD-related pathways. Using proximity labeling of the LD proteome, we identify starch-binding domain-containing protein 1 (STBD1), a glycogen-binding protein involved in glycophagy, as a novel LD component. Further mechanistic investigation shows that STBD1 targets LDs via N-terminal myristoylation and mediates glycogen-LD colocalization. Its depletion decreases LD abundance and impairs both glycophagy and lipophagy, suggesting a critical role of STBD1 in both the biogenesis and autophagic degradation of LDs. Furthermore, STBD1 knockdown alters lipid composition, enhances Ferroptosis sensitivity, and suppresses tumor growth both in vitro and in vivo. Collectively, our findings establish STBD1 as a critical mediator of glycogen-LD crosstalk and highlight its potential as a therapeutic target in ccRCC.

Keywords

CP: Cancer; CP: Metabolism; STBD1; clear cell renal cell carcinoma; ferroptosis; glycogen; glycophagy; lipid droplets; lipophagy; metabolic reprogramming; metabolism.

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