Gene Suppression of Transketolase-Like Protein 1 (TKTL1) Sensitizes Glioma Cells to Hypoxia and Ionizing Radiation

Heller, Sonja; Maurer, Gabriele D.; Wanka, Christina; Hofmann, Ute; Luger, Anna‐Luisa; Bruns, Ines; Steinbach, Joachim P.; Rieger, Johannes

doi:10.3390/ijms19082168

Cited by 15 publications

(18 citation statements)

References 35 publications

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“…In contrast, we observed that the expressions of HIF-1α and also of TKTL-1 (transketolase-like protein 1), induced by hypoxia and HIF-1α, were higher in SCC of the ocular adnexa (including the conjunctiva) in comparison with conjunctival papilloma. Higher HIF-1α and TKTL-1 expression tended to be associated with a worse prognosis [16,20,21]. In the current study, we only stained the initial CIN specimens but not the later CIN recurrences or SCC.…”

Section: Hif and Proexc Expression And Tumor-related Eventsmentioning

confidence: 96%

HIF-1α, HIF-2α, and ProExC: diagnostic or prognostic relevance in conjunctival intraepithelial neoplasia?

Nuessle

Soriano

Boehringer

et al. 2020

Graefes Arch Clin Exp Ophthalmol

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The aim of this study was to investigate HIF-1α, HIF-2α, and ProExC expression in conjunctival intraepithelial neoplasia (CIN), to differentiate between metaplasia and dysplasia, and to access their value as diagnostic and prognostic immunohistochemical markers. Recurrence and progression into SCC (squamous cell carcinoma) were defined as endpoints. Methods Forty-three specimens including CIN I (2), CIN II (9), CIN III (29), with and without metaplasia, and metaplasia alone (3), as well as 21 conjunctival control specimens, were stained with antibodies against HIF-1α, HIF-2α, and ProExC. The percentage of positively stained cells were calculated and used for further analysis. Results The mean percentages of HIF-1α and HIF-2α were not increased in CIN. In comparison, the expressions of these markers were even significantly elevated in control specimens (p < 0.001). Upper epithelial cells in CIN were more often ProExC-positive compared with normal conjunctiva or metaplasia (p = 0.06 and p = 0.07). Cox proportional-hazards analysis was performed for characterization of factors influencing the combined endpoint and showed a significant elevated hazard ratio for staining with ProExC (p = 0.04) compared with HIF-1α (p = 0.26) and HIF-2α (p = 0.49). Conclusion Our study shows that HIF-1α and HIF-2α do not serve as diagnostic or prognostic markers in CIN. ProExC seems to be a potential indicator for CIN, but not a reliable diagnostic marker. However, control specimens occasionally also display a high percentage of ProExC-positive cells and staining over the entire epithelial layer.

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Section: Hif and Proexc Expression And Tumor-related Eventsmentioning

confidence: 96%

HIF-1α, HIF-2α, and ProExC: diagnostic or prognostic relevance in conjunctival intraepithelial neoplasia?

Nuessle

Soriano

Boehringer

et al. 2020

Graefes Arch Clin Exp Ophthalmol

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“…Increased PPP activity induces high levels of ROS. This is counteracted by an adaptive response that is found with the use of chemotherapeutic agents [26,32,246], radiation [247,248,249,250], and oxidative agents [28,239,251]. Drug-resistant cancer cell lines display increased G6PD activity and increased intracellular glutathione concentrations indicative of oxidative PPP.…”

Section: G6pd/ppp As An Anticancer Targetmentioning

confidence: 99%

The Redox Role of G6PD in Cell Growth, Cell Death, and Cancer

Yang

Yen

et al. 2019

Cells

157

132

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The generation of reducing equivalent NADPH via glucose-6-phosphate dehydrogenase (G6PD) is critical for the maintenance of redox homeostasis and reductive biosynthesis in cells. NADPH also plays key roles in cellular processes mediated by redox signaling. Insufficient G6PD activity predisposes cells to growth retardation and demise. Severely lacking G6PD impairs embryonic development and delays organismal growth. Altered G6PD activity is associated with pathophysiology, such as autophagy, insulin resistance, infection, inflammation, as well as diabetes and hypertension. Aberrant activation of G6PD leads to enhanced cell proliferation and adaptation in many types of cancers. The present review aims to update the existing knowledge concerning G6PD and emphasizes how G6PD modulates redox signaling and affects cell survival and demise, particularly in diseases such as cancer. Exploiting G6PD as a potential drug target against cancer is also discussed.

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“…Moreover, the knockdown of TKTL1 augmented the apoptosis of tumor cells by elevating intracellular ROS level. 19 SLC2A3, also known as GLUT3, could affect tumor aggressiveness under hypoxic conditions. 20 ALDOB was also known as fructose-bisphosphate aldolase, and its downregulation was associated with the poor prognosis of patients with gastric cancer.…”

Section: Discussionmentioning

confidence: 99%

Hypoxia-Related Gene-Based Signature Can Evaluate the Tumor Immune Microenvironment and Predict the Prognosis of Colon Adenocarcinoma Patients

He¹,

Ding²,

Cheng³

et al. 2021

IJGM

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Background Colon adenocarcinoma (COAD) is a common gastrointestinal tumor and often occurs in the left colon with a poor prognosis. The progression of COAD is closely related to the tumor microenvironment, especially the hypoxia. Currently, few studies have reported the correlation between hypoxia-related genes and the prognosis of COAD patients. Furthermore, we constructed a prognostic model using four hypoxia-related genes to predict the prognosis of COAD patients. Methods The mRNA expression profiles and corresponding clinicopathological data were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). The string online analysis tool was used to construct a protein–protein interaction network (PPI) of hypoxia-related genes. Kaplan–Meier curve was used to analyze the relationship of hypoxia risk score and the overall survival of COAD patients, and the receiver operating characteristic (ROC) curve was used to assess the reliability. Results We screened out four hypoxia genes, including TKTL1 (transketolase like 1), SLC2A3 (solute carrier family 2 member 3), ALDOB (aldolase, fructose-bisphosphate B) and ENO3 (enolase 3), which were used to construct a hypoxia risk model to predict the overall survival of COAD patients. Besides, we also found that the hypoxia risk score was correlated with the immunosuppression of tumor microenvironment. Conclusion The model we constructed with four survival-related hypoxia genes, including TKTL1, SLC2A3, ALDOB and ENO3, could be used to predict the overall survival of COAD patients with high stability.

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Gene Suppression of Transketolase-Like Protein 1 (TKTL1) Sensitizes Glioma Cells to Hypoxia and Ionizing Radiation

Cited by 15 publications

References 35 publications

HIF-1α, HIF-2α, and ProExC: diagnostic or prognostic relevance in conjunctival intraepithelial neoplasia?

HIF-1α, HIF-2α, and ProExC: diagnostic or prognostic relevance in conjunctival intraepithelial neoplasia?

The Redox Role of G6PD in Cell Growth, Cell Death, and Cancer

Hypoxia-Related Gene-Based Signature Can Evaluate the Tumor Immune Microenvironment and Predict the Prognosis of Colon Adenocarcinoma Patients

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