Glypican-3 Enhances Reprogramming of Glucose Metabolism in Liver Cancer Cells.

Glypican-3(GPC3) is a transmembrane protein which has been found to be frequently overexpressed on the surfaces of liver cancer (LC) cells, which contributes to both the growth and metastasis of LC cells. Recently, the expression of GPC3 has been reported to be inversely associated with glucose meta...

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Publicado en:BioMed Research International pp. 1 - 12
Autores principales: Yao, Gebing, Yin, Jikai, Wang, Qing, Dong, Rui, Lu, Jianguo
Formato: pictorial research tables/charts Journal Article
Publicado: Wiley-Blackwell 11/6/2019
Acceso en línea:Ver este registro en EBSCOhost
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      dt: 11/6/2019
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      pub: Wiley-Blackwell
      place: Malden, Massachusetts
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        10.1155/2019/2560650
        139513359
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        atl: Glypican-3 Enhances Reprogramming of Glucose Metabolism in Liver Cancer Cells.
      aug:
        au:
          Yao, Gebing
          Yin, Jikai
          Wang, Qing
          Dong, Rui
          Lu, Jianguo
        affil: Department of General Surgery, The Second Affiliated Hospital, The Air Force Military Medical University, Xi'an, Shaanxi 710038, China
      sug:
        subj:
          Polysaccharides
          Liver Neoplasms Physiopathology
          Membrane Transport Proteins Physiology
          Blood Glucose Metabolism
          Cell Line, Tumor Physiopathology
          Glycolysis
          Gene Expression
          Mitochondria Physiology
          Peroxisome Proliferator-Activated Receptors
          Neoplasm Metastasis
          Disease Progression
          Human
      ab: Glypican-3(GPC3) is a transmembrane protein which has been found to be frequently overexpressed on the surfaces of liver cancer (LC) cells, which contributes to both the growth and metastasis of LC cells. Recently, the expression of GPC3 has been reported to be inversely associated with glucose metabolism activity in LC patients, suggesting that GPC3 may play a role in the regulation of glucose metabolism in LC. However, the role of GPC3 in glucose metabolism reprogramming, as well as in LC cell growth and metastasis, is unknown. Here, we found that GPC3 significantly contributed to the reprogramming of glucose metabolism in LC cells. On the one hand, GPC3 enhanced the glycolysis of LC cells through upregulation of the glycolytic genes of Glut1, HK2, and LDH-A. On the other hand, GPC3 repressed mitochondrial respiration through downregulation of peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC-1α), which has been well known as a crucial regulator in mitochondrial biogenesis. Mechanistic investigations revealed that HIF-1α was involved in both GPC3-regulated upregulation of glycolytic genes of HK2, PKM2, and Glut1 and downregulation of mitochondrial biogenesis regulator PGC-1α in LC cells. Additionally, GPC3-regulated reprogramming of glucose metabolism played a critical role in the growth and metastasis of LC cells. Conclusion. Our findings demonstrate that GPC3 is a critical regulator of glucose metabolism reprogramming in LC cells, which provides a strong line of evidence for GPC3 as an important therapeutic target to normalize glucose metabolic aberrations responsible for LC progression.
      pubtype: Academic Journal
      doctype:
        pictorial
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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