Glucose transporter 4: Insulin response mastermind, glycolysis catalyst and treatment direction for cancer progression

Chang, Yu‐Chan; Chan, Ming‐Hsien; Yang, Yujuan; Li, Chien‐Hsiu; Hsiao, Michael

doi:10.1016/j.canlet.2023.216179

Cited by 22 publications

(9 citation statements)

References 159 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Additionally, cancer cells utilize VM, a biological process that mimics blood vessels and connects to normal vascular endothelial cells, to obtain additional nutrients and oxygen [ 51 , 52 ]. Therefore, the Warburg effect and VM are two complementary molecular processes by which cancer cells respond to the anoxic microenvironment [ 24 , 25 , 53 ]. Through the application of IP mass spectrometry, we successfully identified PKM2 as the protein that interacts with ESM1.…”

Section: Discussionmentioning

confidence: 99%

ESM1 enhances fatty acid synthesis and vascular mimicry in ovarian cancer by utilizing the PKM2-dependent warburg effect within the hypoxic tumor microenvironment

Zhang,

Ouyang,

Gao

et al. 2024

Mol Cancer

View full text Add to dashboard Cite

Background The hypoxic tumor microenvironment is a key factor that promotes metabolic reprogramming and vascular mimicry (VM) in ovarian cancer (OC) patients. ESM1, a secreted protein, plays an important role in promoting proliferation and angiogenesis in OC. However, the role of ESM1 in metabolic reprogramming and VM in the hypoxic microenvironment in OC patients has not been determined. Methods Liquid chromatography coupled with tandem MS was used to analyze CAOV3 and OV90 cells. Interactions between ESM1, PKM2, UBA2, and SUMO1 were detected by GST pull-down, Co-IP, and molecular docking. The effects of the ESM1-PKM2 axis on cell glucose metabolism were analyzed based on an ECAR experiment. The biological effects of the signaling axis on OC cells were detected by tubule formation, transwell assay, RT‒PCR, Western blot, immunofluorescence, and in vivo xenograft tumor experiments. Results Our findings demonstrated that hypoxia induces the upregulation of ESM1 expression through the transcription of HIF-1α. ESM1 serves as a crucial mediator of the interaction between PKM2 and UBA2, facilitating the SUMOylation of PKM2 and the subsequent formation of PKM2 dimers. This process promotes the Warburg effect and facilitates the nuclear translocation of PKM2, ultimately leading to the phosphorylation of STAT3. These molecular events contribute to the promotion of ovarian cancer glycolysis and vasculogenic mimicry. Furthermore, our study revealed that Shikonin effectively inhibits the molecular interaction between ESM1 and PKM2, consequently preventing the formation of PKM2 dimers and thereby inhibiting ovarian cancer glycolysis, fatty acid synthesis and vasculogenic mimicry. Conclusion Our findings demonstrated that hypoxia increases ESM1 expression through the transcriptional regulation of HIF-1α to induce dimerization via PKM2 SUMOylation, which promotes the OC Warburg effect and VM.

show abstract

Section: Discussionmentioning

confidence: 99%

ESM1 enhances fatty acid synthesis and vascular mimicry in ovarian cancer by utilizing the PKM2-dependent warburg effect within the hypoxic tumor microenvironment

Zhang,

Ouyang,

Gao

et al. 2024

Mol Cancer

View full text Add to dashboard Cite

show abstract

“…AMP-activated protein kinase (AMPK) is a widely distributed serine/threonine protein kinase involved in a range of metabolic processes that play a vital role in energy metabolism and catabolism in WAT [ 28 , 35 , 36 ]. GLUT-4 is a key glucose transporter that promotes the use of extracellular glucose by insulin-sensitive cells to maintain blood glucose homeostasis [ 37 , 38 ]. In other words, a decrease in GLUT-4 in skeletal muscle and lipoprotein expression and the inhibition of the translocation of GLUT4 to the cell surface lead to insufficient glucose transport and hence insulin resistance [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

Anti-Obesity Effect and Mechanism of Chitooligosaccharides Were Revealed Based on Lipidomics in Diet-Induced Obese Mice

et al. 2023

View full text Add to dashboard Cite

Chitooligosaccharide (COS) is a natural product from the ocean, and while many studies have reported its important role in metabolic diseases, no study has systematically elaborated the anti-obesity effect and mechanism of COS. Herein, COSM (MW ≤ 3000 Da) was administered to diet-induced obese mice by oral gavage once daily for eight weeks. The results show that COSM administration reduced body weight; slowed weight gain; reduced serum Glu, insulin, NEFA, TC, TG, and LDL-C levels; increased serum HSL and HDL-C levels; improved inflammation; and reduced lipid droplet size in adipose tissue. Further lipidomic analysis of adipose tissue revealed that 31 lipid species are considered to be underlying lipid biomarkers in COS therapy. These lipids are mainly enriched in pathways involving insulin resistance, thermogenesis, cholesterol metabolism, glyceride metabolism and cyclic adenosine monophosphate (cAMP), which sheds light on the weight loss mechanism of COS. The Western blot assay demonstrated that COSM intervention can improve insulin resistance, inhibit de novo synthesis, and promote thermogenesis and β-oxidation in mitochondria by the AMPK pathway, thereby alleviating high-fat diet-induced obesity. In short, our study can provide a more comprehensive direction for the application of COS in obesity based on molecular markers.

show abstract

“…Although hyperglycemia is known risk factor to promote tumor growth ( 124 , 125 ), KD indeed inhibit glucose uptake in cancer cells by lowering their glucose availability ( 126 ). Moreover, low levels of insulin and IGF-1 suppress the activation of PI3K/Akt/GLUT4 signaling pathway, reducing the glucose uptake and downregulating the membrane translocation of glucose transporters ( 127 – 129 ) ( Figure 4A ). Additionally, it also inhibits the insulin-related down-stream signaling molecules such as NF-κB, and vascular endothelial growth factor (VEGF) to exert a pro-apoptosis and anti-angiogenesis for cancers ( 130 , 131 ).…”

Section: Ketogenic Dietmentioning

confidence: 99%

Review of dietary patterns and gastric cancer risk: epidemiology and biological evidence

Pu,

Feng,

Tang

et al. 2024

Front. Oncol.

View full text Add to dashboard Cite

Due to rapid research expansion on dietary factors and development of cancer prevention guidelines, the field of dietary pattern and its relationship to cancer risk has gained more focus. Numerous epidemiology studies have reported associations between Gastric Cancer (GC) and both data-driven posteriori dietary pattern and priori dietary pattern defined by predetermined dietary indexes. As dietary patterns have evolved, a series of patterns based on biological markers has advanced, offering deeper insights into the relationship between diet and the risk of cancer. Although researches on dietary patterns and cancer risk are booming, there is limited body of literature focusing specifically on GC. In this study, we compare the similarities and differences among the specific components of dietary patterns and indices, summarize current state of knowledge regarding dietary patterns related to GC and illustrate their potential mechanisms for GC prevention. In conclusion, we offer suggestions for future research based on the emerging themes within this rapidly evolving field.

show abstract

Glucose transporter 4: Insulin response mastermind, glycolysis catalyst and treatment direction for cancer progression

Cited by 22 publications

References 159 publications

ESM1 enhances fatty acid synthesis and vascular mimicry in ovarian cancer by utilizing the PKM2-dependent warburg effect within the hypoxic tumor microenvironment

ESM1 enhances fatty acid synthesis and vascular mimicry in ovarian cancer by utilizing the PKM2-dependent warburg effect within the hypoxic tumor microenvironment

Anti-Obesity Effect and Mechanism of Chitooligosaccharides Were Revealed Based on Lipidomics in Diet-Induced Obese Mice

Review of dietary patterns and gastric cancer risk: epidemiology and biological evidence

Contact Info

Product

Resources

About