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  2. Hsp90 Promotes Gastric Cancer Cell Metastasis and Stemness by Regulating the Regional Distribution of Glycolysis-Related Metabolic Enzymes in the Cytoplasm

Hsp90 Promotes Gastric Cancer Cell Metastasis and Stemness by Regulating the Regional Distribution of Glycolysis-Related Metabolic Enzymes in the Cytoplasm

  • Adv Sci (Weinh). 2024 Jun 14:e2310109. doi: 10.1002/advs.202310109.
Shiya Liu 1 Gaigai Shen 1 Xuanyu Zhou 2 Lixin Sun 1 Long Yu 1 Yuanting Cao 1 Xiong Shu 3 Yuliang Ran 1
Affiliations

Affiliations

  • 1 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.
  • 2 Department of Epidemiology & Population Health, Stanford University of Medicine, Stanford, CA, 94305, USA.
  • 3 Beijing Research Institute of Orthopaedics and Traumatology, Beijing Jishuitan Hospital, Capital Medical University, Beijing, 100035, China.
Abstract

Heat-shock protein 90 (HSP90) plays a crucial role in tumorigenesis and tumor progression; however, its mechanism of action in gastric Cancer (GC) remains unclear. Here, the role of HSP90 in GC metabolism is the focus of this research. High expression of HSP90 in GC tissues can interact with glycolysis, collectively affecting prognosis in clinical samples. Both in vitro and in vivo experiments demonstrate that HSP90 is able to regulate the migration and stemness properties of GC cells. Metabolic phenotype analyses indicate that HSP90 influences glycolytic metabolism. Mechanistically, HSP90 interacts with glycolysis-related Enzymes, forming multienzyme complexes to enhance glycolysis efficiency and yield. Additionally, HSP90 binds to cytoskeleton-related proteins, regulating the regional distribution of glycolytic Enzymes at the cell margin and lamellar pseudopods. This effect could lead to a local increase in efficient energy supply from glycolysis, further promoting epithelial-mesenchymal transition (EMT) and metastasis. In summary, HSP90, through its interaction with metabolic Enzymes related to glycolysis, forms multi-enzyme complexes and regulates regional distribution of glycolysis by dynamic cytoskeletal adjustments, thereby promoting the migration and stemness of GC cells. These conclusions also support the potential for a combined targeted approach involving HSP90, glycolysis, and the Cytoskeleton in clinical therapy.

Keywords

Hsp90; combination therapy; glycolysis; multienzyme complex; regionalized distribution.

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