2. Academic Validation
  3. Deficiency of TOP1MT enhances glycolysis through the stimulation of PDK4 expression in gastric cancer

Deficiency of TOP1MT enhances glycolysis through the stimulation of PDK4 expression in gastric cancer

  • Cancer Metab. 2024 Jan 10;12(1):2. doi: 10.1186/s40170-024-00330-w.
Hongqiang Wang # 1,  Xutao Sun # 2,  Chen Yang # 2,  Ziqi Li 3,  Danwen Jin 4,  Wenwen Zhu 1,  Ze Yu 5 6
Affiliations

Affiliations

  • 1 Cancer Chemotherapy Center, Zhoushan Hospital, Wenzhou Medical University, Zhoushan, China.
  • 2 Department of General Surgery, Zhoushan Hospital, Wenzhou Medical University, No. 739 Dingshen Road, Lincheng New District, Zhoushan, Zhejiang, 316021, China.
  • 3 The Laboratory of Cytobiology and Molecular Biology, Zhoushan Hospital, Wenzhou Medical University, Zhoushan, China.
  • 4 Department of Pathology, Zhoushan Hospital, Wenzhou Medical University, Zhoushan, China.
  • 5 Department of General Surgery, Zhoushan Hospital, Wenzhou Medical University, No. 739 Dingshen Road, Lincheng New District, Zhoushan, Zhejiang, 316021, China. zeyunfu@163.com.
  • 6 The Laboratory of Cytobiology and Molecular Biology, Zhoushan Hospital, Wenzhou Medical University, Zhoushan, China. zeyunfu@163.com.
  • # Contributed equally.
PMID: 38200513 DOI: 10.1186/s40170-024-00330-w
Abstract

Background: Abnormal glucose metabolism is one of the determinants of maintaining malignant characteristics of Cancer. Targeting Cancer metabolism is regarded as a new strategy for Cancer treatment. Our previous studies have found that TOP1MT is a crucial gene that inhibits glycolysis and cell metastasis of gastric Cancer (GC) cells, but the mechanism of its regulation of glycolysis remains unclear.

Methods: Transcriptome sequencing data, clinic-pathologic features of GC from a variety of public databases, and WGCNA were used to identify novel targets of TOP1MT. Immunohistochemical results of 250 patients with GC were used to analyze the relative expression relationship between TOP1MT and PDK4. The function of TOP1MT was investigated by migration assays and sea-horse analysis in vitro.

Results: We discovered a mitochondrial Topoisomerase I, TOP1MT, which correlated with a higher risk of metastasis. Functional experiments revealed that TOP1MT deficiency promotes cell migration and glycolysis through increasing PDK4 expression. Additionally, the stimulating effect of TOP1MT on glycolysis may be effectively reversed by PDK4 inhibitor M77976.

Conclusions: In brief, our work demonstrated the critical function of TOP1MT in the regulation of glycolysis by PDK4 in gastric Cancer. Inhibiting glycolysis and limiting tumor metastasis in GC may be accomplished by suppressing PDK4.

Keywords

Cell migration; Gastric cancer; Glycolysis; PDK4; TOP1MT.

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