Structure, regulation, and biological functions of TIGAR and its role in diseases

Tang, Jie; Chen, Lei; Qin, Zheng‐Hong; Sheng, Rui

doi:10.1038/s41401-020-00588-y

Cited by 42 publications

(40 citation statements)

References 92 publications

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“…Under hypoxia HK2 can form a complex on the mitochondrial surface with TIGAR, a fructose-2,6-bisphosphatase that inhibits glycolysis and promotes PPP [ 84 ]. The HK2/TIGAR complex lowers mitochondrial ROS levels, stimulates HK2 activity and protects colorectal carcinoma cells from death.…”

Section: Hk2 On Mitochondria Of Neoplastic Cells: Maintaining the Bad Guy In Perfect Shapementioning

confidence: 99%

Hexokinase 2 in Cancer: A Prima Donna Playing Multiple Characters

Ciscato

Ferrone

Masgras

et al. 2021

IJMS

123

103

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Hexokinases are a family of ubiquitous exose-phosphorylating enzymes that prime glucose for intracellular utilization. Hexokinase 2 (HK2) is the most active isozyme of the family, mainly expressed in insulin-sensitive tissues. HK2 induction in most neoplastic cells contributes to their metabolic rewiring towards aerobic glycolysis, and its genetic ablation inhibits malignant growth in mouse models. HK2 can dock to mitochondria, where it performs additional functions in autophagy regulation and cell death inhibition that are independent of its enzymatic activity. The recent definition of HK2 localization to contact points between mitochondria and endoplasmic reticulum called Mitochondria Associated Membranes (MAMs) has unveiled a novel HK2 role in regulating intracellular Ca2+ fluxes. Here, we propose that HK2 localization in MAMs of tumor cells is key in sustaining neoplastic progression, as it acts as an intersection node between metabolic and survival pathways. Disrupting these functions by targeting HK2 subcellular localization can constitute a promising anti-tumor strategy.

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Section: Hk2 On Mitochondria Of Neoplastic Cells: Maintaining the Bad Guy In Perfect Shapementioning

confidence: 99%

Hexokinase 2 in Cancer: A Prima Donna Playing Multiple Characters

Ciscato

Ferrone

Masgras

et al. 2021

IJMS

123

103

View full text Add to dashboard Cite

show abstract

“…When TIGAR's function is impaired, ROS levels increase, triggering autophagy induction. Nevertheless, it is unlikely to have an effect on the mTOR pathway (Tang et al, 2021a). It is most likely to have a non-mTOR-mediated metabolic pathway as TIGAR does not appear to have a significant impact on mTOR signaling.…”

Section: P53 Signaling Targets As a Cancer Therapy Via Modulation Of Autophagymentioning

confidence: 99%

p53 Modulation of Autophagy Signaling in Cancer Therapies: Perspectives Mechanism and Therapeutic Targets

Rahman

Park

Rahman

et al. 2022

Front. Cell Dev. Biol.

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The key tumor suppressor protein p53, additionally known as p53, represents an attractive target for the development and management of anti-cancer therapies. p53 has been implicated as a tumor suppressor protein that has multiple aspects of biological function comprising energy metabolism, cell cycle arrest, apoptosis, growth and differentiation, senescence, oxidative stress, angiogenesis, and cancer biology. Autophagy, a cellular self-defense system, is an evolutionarily conserved catabolic process involved in various physiological processes that maintain cellular homeostasis. Numerous studies have found that p53 modulates autophagy, although the relationship between p53 and autophagy is relatively complex and not well understood. Recently, several experimental studies have been reported that p53 can act both an inhibitor and an activator of autophagy which depend on its cellular localization as well as its mode of action. Emerging evidences have been suggested that the dual role of p53 which suppresses and stimulates autophagy in various cencer cells. It has been found that p53 suppression and activation are important to modulate autophagy for tumor promotion and cancer treatment. On the other hand, activation of autophagy by p53 has been recommended as a protective function of p53. Therefore, elucidation of the new functions of p53 and autophagy could contribute to the development of novel therapeutic approaches in cancer biology. However, the underlying molecular mechanisms of p53 and autophagy shows reciprocal functional interaction that is a major importance for cancer treatment and manegement. Additionally, several synthetic drugs and phytochemicals have been targeted to modulate p53 signaling via regulation of autophagy pathway in cancer cells. This review emphasizes the current perspectives and the role of p53 as the main regulator of autophagy-mediated novel therapeutic approaches against cancer treatment and managements.

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“…The abnormal expression of the tumor suppressor gene p53 is one of the factors that affects the rate of aerobic glycolysis in tumors. The two downstream transcription targets of p53 are TP53-induced glycolysis and apoptosis regulator (TIGAR) and cytochrome oxidase 2 (synthesis of cytochrome oxidase 2, SCO2) [22,23]. The TIGAR sequence is similar to that of the phosphofructokinase (PFK), which can hydrolyze fructose 2,6-diphosphate, thereby inhibiting aerobic glycolysis.…”

Section: Discussionmentioning

confidence: 99%

Effect of Linc-00475 Regulation of p53 on Glycolysis and Survival in Gastric Cancer

Zhang

Wang

2021

Preprint

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Background: Abnormal glucose metabolism leading to tumor proliferation and metastasis is an important area of interest in cancer treatment. The purpose of this study was to investigate the effects of clinical expression of glucose metabolism-related genes Linc-00475 and p53 on glycolysis and survival.Methods: A key differential gene Linc-00475 was screened using a metabolic database, and its downstream gene, p53, was predicted. A total of 107 gastric cancer tissue samples from patients diagnosed at our center between 2011 and 2013 were selected. The expression levels of Linc-00475 and p53 were detected via in situ hybridization or immunohistochemistry. Chi-square test was used to analyze the relationship between Linc-00475 and p53 expression and clinicopathological factors. Kaplan-Meier method and log rank test were used to analyze patients’ overall survival. To determine the effect of Linc-00475 on glycolysis, qRT-PCR and western blot were utilized to evaluate the regulatory relationship between Linc-00475 and p53.Results: High expression of Linc-00475 (P < 0.001) and low expression of p53 (P < 0.01) were associated with poor prognosis. There was a negative correlation between the expression of Linc-00475 and p53 in gastric cancer (Pearson's coefficient test, r = -0.405; P < 0.001). The co-expression of high-level Linc-00475 and low-level p53 can thus be used as an independent prognostic factor (P = 0.001). Linc-00475 was also shown to regulate aerobic glycolysis. Western blot and qRT-PCR demonstrated that Linc-00475 regulates the expression of p53.Conclusion: The co-expression of Linc-00475 and p53 can be used as a reference index for evaluating the prognosis of gastric cancer. Linc-00475 regulates p53, thereby affecting glycolysis.

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Structure, regulation, and biological functions of TIGAR and its role in diseases

Cited by 42 publications

References 92 publications

Hexokinase 2 in Cancer: A Prima Donna Playing Multiple Characters

Hexokinase 2 in Cancer: A Prima Donna Playing Multiple Characters

p53 Modulation of Autophagy Signaling in Cancer Therapies: Perspectives Mechanism and Therapeutic Targets

Effect of Linc-00475 Regulation of p53 on Glycolysis and Survival in Gastric Cancer

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