Hexokinases in cancer and other pathologies

Guo, Dong; Meng, Ying; Jiang, Xiaoming; Lu, Zhimin

doi:10.1016/j.cellin.2023.100077

Cited by 26 publications

(18 citation statements)

References 122 publications

(138 reference statements)

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“… 801 HK2 expression is correlated with advanced-stage and high-grade ovarian cancer. 798 HK2 downregulation inhibits tumor occurrence. 802 Thus, HK2 is a meaningful prognostic tumor biomarker and a potential tumor treatment target.…”

Section: Classification Of Tumor Biomarkersmentioning

confidence: 99%

“…The hexokinases family has five isoforms in mammals including hexokinase 1–4 (HK1, HK2, HK3, HK4), and HKDC1. 798 HK2 is the most active isozyme of the hexokinase family. 799 In addition to being expressed in the muscle and heart, 798 HK2 has been evaluated in various cancers, and is induced solely or synergistically by HIF-1 and MYC.…”

Section: Classification Of Tumor Biomarkersmentioning

confidence: 99%

“… 798 HK2 is the most active isozyme of the hexokinase family. 799 In addition to being expressed in the muscle and heart, 798 HK2 has been evaluated in various cancers, and is induced solely or synergistically by HIF-1 and MYC. 800 An analysis of 21 studies with 2532 patients has revealed that HK2 overexpression is significantly associated with worse OS and PFS in solid tumors.…”

Section: Classification Of Tumor Biomarkersmentioning

confidence: 99%

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Tumor biomarkers for diagnosis, prognosis and targeted therapy

Zhou,

Tao,

Qiu

et al. 2024

Sig Transduct Target Ther

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Tumor biomarkers, the substances which are produced by tumors or the body’s responses to tumors during tumorigenesis and progression, have been demonstrated to possess critical and encouraging value in screening and early diagnosis, prognosis prediction, recurrence detection, and therapeutic efficacy monitoring of cancers. Over the past decades, continuous progress has been made in exploring and discovering novel, sensitive, specific, and accurate tumor biomarkers, which has significantly promoted personalized medicine and improved the outcomes of cancer patients, especially advances in molecular biology technologies developed for the detection of tumor biomarkers. Herein, we summarize the discovery and development of tumor biomarkers, including the history of tumor biomarkers, the conventional and innovative technologies used for biomarker discovery and detection, the classification of tumor biomarkers based on tissue origins, and the application of tumor biomarkers in clinical cancer management. In particular, we highlight the recent advancements in biomarker-based anticancer-targeted therapies which are emerging as breakthroughs and promising cancer therapeutic strategies. We also discuss limitations and challenges that need to be addressed and provide insights and perspectives to turn challenges into opportunities in this field. Collectively, the discovery and application of multiple tumor biomarkers emphasized in this review may provide guidance on improved precision medicine, broaden horizons in future research directions, and expedite the clinical classification of cancer patients according to their molecular biomarkers rather than organs of origin.

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Section: Classification Of Tumor Biomarkersmentioning

confidence: 99%

Section: Classification Of Tumor Biomarkersmentioning

confidence: 99%

Section: Classification Of Tumor Biomarkersmentioning

confidence: 99%

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Tumor biomarkers for diagnosis, prognosis and targeted therapy

Zhou,

Tao,

Qiu

et al. 2024

Sig Transduct Target Ther

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“…The HK enzyme catalyzes the initial step of glucose metabolism, converting glucose into glucose-6-phosphate (G6P). Mammalian organisms exhibit the expression of various isoforms of HK, specifically HK1, HK2, HK3, and HK4 [ 49 ]. Among these isoforms, HK2 assumes a crucial dual function in the regulation of glucose metabolism in microglial cells.…”

Section: Glucose Metabolism Of Microglia In Neuroinflammationmentioning

confidence: 99%

“…It facilitates the maintenance of the mitochondrial membrane electrochemical potential difference (Δψ), preventing excessive generation of ROS and ROS-induced immune responses[ 51 ]. Deficiency of HK2 substantially promotes microglia activation, phagocytosis, and inflammatory responses [ 49 , 51 ]. Thus, understanding HK2's role in microglia homeostasis and disease development will illuminate CNS microglia metabolism.…”

Section: Glucose Metabolism Of Microglia In Neuroinflammationmentioning

confidence: 99%

Glycometabolic Reprogramming of Microglia in Neurodegenerative Diseases: Insights from Neuroinflammation

Huang,

Wang,

Chen

et al. 2023

Aging and disease

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Neurodegenerative diseases (ND) are conditions defined by progressive deterioration of the structure and function of the nervous system. Some major examples include Alzheimer's disease (AD), Parkinson's disease (PD), and Amyotrophic lateral sclerosis (ALS). These diseases lead to various dysfunctions, like impaired cognition, memory, and movement. Chronic neuroinflammation may underlie numerous neurodegenerative disorders. Microglia, an important immunocell in the brain, plays a vital role in defending against neuroinflammation. When exposed to different stimuli, microglia are activated and assume different phenotypes, participating in immune regulation of the nervous system and maintaining tissue homeostasis. The immunological activity of activated microglia is affected by glucose metabolic alterations. However, in the context of chronic neuroinflammation, specific alterations of microglial glucose metabolism and their mechanisms of action remain unclear. Thus, in this paper, we review the glycometabolic reprogramming of microglia in ND. The key molecular targets and main metabolic pathways are the focus of this research. Additionally, this study explores the mechanisms underlying microglial glucose metabolism reprogramming in ND and offers an analysis of the most recent therapeutic advancements. The ultimate aim is to provide insights into the development of potential treatments for ND.

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Inhibition of Yeast Hexokinase by Acyl Glucosides of Phloretin and its Implication in the Warburg Effect

Cervantes,

Fernandez‐Arrojo,

Coscolin

et al. 2024

ChemistrySelect

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Contrary to differentiated cells, cancer cells predominantly convert glucose to lactate even under conditions of adequate oxygen supply (“Warburg effect”). The initial enzyme implicated in this route is hexokinase, which transforms D‐glucose into D‐glucose‐6‐phosphate. We proposed the use of different polyphenols (resveratrol, epigallocatechin gallate, pterostilbene, phloretin) and their derivatives (α‐glucosides and acylated α‐glucosides) to inhibit this enzyme. For this study, we used Saccharomyces cerevisiae hexokinase, whose two isoforms show high resemblance at the active site with human hexokinase HK2. To monitor the reactions, a method of anion‐exchange chromatography coupled with pulsed amperometric detection (HPAEC‐PAD) was developed. Remarkably, most of the assayed compounds inhibited the enzyme more than 50 % in the standard assay. Among them, phloretin 4’‐O‐(6’’‐O‐octanoyl)‐α‐D‐glucopyranoside showed the highest inhibition and was studied in depth to determine the inhibition pattern and inhibition constant. The Ki for glucose was calculated to be 22.1±0.4 μM. Computational models of inhibition were carried out with the three molecules displaying the highest inhibition, and correlated adequately with the observed inhibitory effects on the enzyme. The inhibitory effect of several of the assayed polyphenols on hexokinase and their lack of toxicity renders them promising candidates as adjuvant drugs for cancer therapy.

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Hexokinases in cancer and other pathologies

Cited by 26 publications

References 122 publications

Tumor biomarkers for diagnosis, prognosis and targeted therapy

Tumor biomarkers for diagnosis, prognosis and targeted therapy

Glycometabolic Reprogramming of Microglia in Neurodegenerative Diseases: Insights from Neuroinflammation

Inhibition of Yeast Hexokinase by Acyl Glucosides of Phloretin and its Implication in the Warburg Effect

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