Up-regulation of key glycolysis proteins in cancer development

Nowak, Nicole; Kulma, Anna; Gutowicz, Jan

doi:10.1515/biol-2018-0068

Cited by 37 publications

(36 citation statements)

References 80 publications

(150 reference statements)

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“…Being structurally similar, the four isoforms vary in expression pattern, cellular localization and properties in regulation. The dominantly expressed among these is HK II which is found to be up-regulated in most of the tissues [16]. Hexokinase II was found to be over-expressed in most cancers leading to enhanced glycolytic rate, which is a phenotype for cancer cells [17].…”

Section: Introductionmentioning

confidence: 99%

PI3K-AKT Pathway Modulation by Thymoquinone Limits Tumor Growth and Glycolytic Metabolism in Colorectal Cancer

Karim

Burzangi

Ahmad

et al. 2022

IJMS

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Colorectal cancer (CRC) is the third leading cause of death in men and the fourth in women worldwide and is characterized by deranged cellular energetics. Thymoquinone, an active component from Nigella sativa, has been extensively studied against cancer, however, its role in affecting deregulated cancer metabolism is largely unknown. Further, the phosphoinositide 3-kinase (PI3K) pathway is one of the most activated pathways in cancer and its activation is central to most deregulated metabolic pathways for supporting the anabolic needs of growing cancer cells. Herein, we provide evidence that thymoquinone inhibits glycolytic metabolism (Warburg effect) in colorectal cancer cell lines. Further, we show that such an abrogation of deranged cell metabolism was due, at least in part, to the inhibition of the rate-limiting glycolytic enzyme, Hexokinase 2 (HK2), via modulating the PI3/AKT axis. While overexpression of HK2 showed that it is essential for fueling glycolytic metabolism as well as sustaining tumorigenicity, its pharmacologic and/or genetic inhibition led to a reduction in the observed effects. The results decipher HK2 mediated inhibitory effects of thymoquinone in modulating its glycolytic metabolism and antitumor effects. In conclusion, we provide evidence of metabolic perturbation by thymoquinone in CRC cells, highlighting its potential to be used/repurposed as an antimetabolite drug, though the latter needs further validation utilizing other suitable cell and/or preclinical animal models.

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Section: Introductionmentioning

confidence: 99%

PI3K-AKT Pathway Modulation by Thymoquinone Limits Tumor Growth and Glycolytic Metabolism in Colorectal Cancer

Karim

Burzangi

Ahmad

et al. 2022

IJMS

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“…In adenocarcinoma, GLUT1 and GLUT3 expression correlate with maximum standardized uptake value (SUV max), but no such correlation was observed for SCC. Neither GLUT1 or GLUT3 expression was correlated with tumor size or 18 F-FDG uptake. 131 RNA-seq and FDG of lung squamous cell carcinoma (LUSC) from patients who underwent surgical resection in correlation to glucose transporters by RNA-seq and immune cell enrichment score (ImmuneScore).…”

Section: Lung Cancersmentioning

confidence: 82%

Glucose transporters as markers of diagnosis and prognosis in cancer diseases

Szablewski¹

2022

Oncol Rev

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Glucose is a main metabolic substrate, which plays a role as a source of energy and a substrate in several processes. Cell membrane is lipophilic, whereas monosaccharides are hydrophilic. Therefore, lipid bilayer is impermeable for these substances and they need specific carrier proteins. Glucose metabolism in cancer cells differs from this process in normal cells. Cancer cells prefer the process of glycolysis, which generates less molecules of ATP than complete oxidative breakdown, therefore cancer cells need more molecules of glucose. Increased uptake of glucose is due to changes in expression of glucose transporters. Several glucose transporters are overexpressed in cancer cells, however, there are also observed decreased levels of these proteins in cancer cells. There are observed specific correlations between cancer and expression of glucose carrier proteins. Therefore, changes in expression of glucose transporters in cancers may be treated as a marker of diagnosis and/or prognosis for cancer patients.

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“…As described earlier, cancer cells cause changes in the expression of genes that code HIF-1, hexokinase 2 (HK2), phosphoglucose isomerase (PG), glyceraldehyde 3-phosphate dehydrogenase, and glucose transporters that are involved in the hypoxic conditions within tumors. Therefore, it is suggested that hypoxia-regulated genes may be a therapeutic target in anticancer therapy [46]. GLUT proteins, such as GLUT1 and GLUT3, and sodiumdependent glucose symporters, such as SGLT1 and SGLT2, are overexpressed in cancers.…”

Section: Glut Proteins As a Target In Anticancer Therapymentioning

confidence: 99%

Glucose Transporters as a Target for Anticancer Therapy

Pliszka

Szablewski

2021

Cancers

118

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Tumor growth causes cancer cells to become hypoxic. A hypoxic condition is a hallmark of cancer. Metabolism of cancer cells differs from metabolism of normal cells. Cancer cells prefer the process of glycolysis as a source of ATP. Process of glycolysis generates only two molecules of ATP per one molecule of glucose, whereas the complete oxidative breakdown of one molecule of glucose yields 36 molecules of ATP. Therefore, cancer cells need more molecules of glucose in comparison with normal cells. Increased uptake of glucose by these cells is due to overexpression of glucose transporters, especially GLUT1 and GLUT3, that are hypoxia responsive, as well as other glucose transport proteins. Increased expression of these carrier proteins may be used in anticancer therapy. This phenomenon is used in diagnostic techniques such as FDG-PET. It is also suggested, and there are observations, that therapeutic inhibition of glucose transporters may be a method in treatment of cancer patients. On the other hand, there are described cases, in which upregulation of glucose transporters, as, for example, NIS, which is used in radioiodine therapy, can help patients with cancer. The aim of this review is the presentation of possibilities, and how glucose transporters can be used in anticancer therapy.

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Up-regulation of key glycolysis proteins in cancer development

Cited by 37 publications

References 80 publications

PI3K-AKT Pathway Modulation by Thymoquinone Limits Tumor Growth and Glycolytic Metabolism in Colorectal Cancer

PI3K-AKT Pathway Modulation by Thymoquinone Limits Tumor Growth and Glycolytic Metabolism in Colorectal Cancer

Glucose transporters as markers of diagnosis and prognosis in cancer diseases

Glucose Transporters as a Target for Anticancer Therapy

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