Hyperoxia induces glucose metabolism reprogramming and intracellular acidification by suppressing MYC/MCT1 axis in lung cancer

Liu, Xiucheng; Qin, Hao; Zhang, Li; Jia, Caili; Chao, Zhixiang; Qin, Xichun; Zhang, Hao; Chang, Chen

doi:10.1016/j.redox.2023.102647

Cited by 7 publications

(5 citation statements)

References 41 publications

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“…To survive in a harsh environment (e.g., an environment in which the cells are detached from the primary site and facing energy deprivation), tumor cells often undergo adjustments in energy utilization ( 42 - 44 ). The Warburg effect, or aerobic glycolysis, has historically referred to the metabolic reprogramming of malignant cells, and represents the preferred mode by which tumors acquire energy for survival ( 45 , 46 ).…”

Section: Discussionmentioning

confidence: 99%

ENO2 promotes anoikis resistance in anaplastic thyroid cancer by maintaining redox homeostasis

Zhang,

Ji,

Wang

2024

Gland Surg

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Background Anoikis presents a significant barrier in the metastasis of cancer. As the most aggressive type of thyroid cancer, anaplastic thyroid cancer (ATC) exhibits a high risk of metastasis and is characterized by high mortality. Therefore, investigating the molecular mechanisms of anoikis resistance in ATC is important for devising therapeutic targets in clinical research. Methods Differentially Expressed Genes were screened in ATC cells under attached and detached culture conditions with RNA-seq. Investigate the impact of enolase 2 (ENO2) on apoptosis and spheroid formation by gain and loss of function. Changes of reactive oxygen species (ROS), glutathione (GSH) and nicotinamide adenine dinucleotide phosphate (NADPH) were detected to assess redox balance. The transcriptional regulatory role of signal transducer and activator of transcription 1 (STAT1) on ENO2 was validated through Dual-Luciferase Reporter Gene Assay. Explore the impact of ENO2 expression on the formation of lung metastases in nude mice. Results We found that the glycolysis process was activated in detached ATC cells. Several genes in the glycolysis process, particularly ENO2 , a member of the enolase superfamily was upregulated in ATC cells cultured in suspension. The upregulation of ENO2 enabled the maintenance of redox balance by supplying GSH and NADPH, thereby preventing cells from undergoing anoikis. In terms of mechanism, the expression of STAT1 was enhanced in anoikis resistance cells, which in turn positively regulated the expression of ENO2. In vivo , ENO2-suppressed ATC cells resulted in a significantly lower rate of lung colonization compared to control ATC cells. Conclusions Stable expression of ENO2 and the maintenance of redox balance played a pivotal role in facilitating anoikis resistance of ATC.

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Section: Discussionmentioning

confidence: 99%

ENO2 promotes anoikis resistance in anaplastic thyroid cancer by maintaining redox homeostasis

Zhang,

Ji,

Wang

2024

Gland Surg

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“…MCT1, also known as SLC16A1, is highly upregulated in various tumor tissues and plays a crucial role in exporting lactate to the TME. [ 9 , 32 , 33 ] However, the post‐transcriptional regulation of MCT1 has been limited to miRNAs, [ 34 , 35 , 36 ] and its PTM has not been fully elucidated. Recent studies have highlighted the significance of PTMs in regulating protein stability, and lysine methylation has been shown to affect the stability of many key non‐histone proteins.…”

Section: Discussionmentioning

confidence: 99%

SETDB1 Methylates MCT1 Promoting Tumor Progression by Enhancing the Lactate Shuttle

She

Rao

et al. 2023

Advanced Science

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MCT1 is a critical protein found in monocarboxylate transporters that plays a significant role in regulating the lactate shuttle. However, the post‐transcriptional modifications that regulate MCT1 are not clearly identified. In this study, it is reported that SETDB1 interacts with MCT1, leading to its stabilization. These findings reveal a novel post‐translational modification of MCT1, in which SETDB1 methylation occurs at K473 in vitro and in vivo. This methylation inhibits the interaction between MCT1 and Tollip, which blocks Tollip‐mediated autophagic degradation of MCT1. Furthermore, MCT1 K473 tri‐methylation promotes tumor glycolysis and M2‐like polarization of tumor‐associated macrophages in colorectal cancer (CRC), which enhances the lactate shuttle. In clinical studies, MCT1 K473 tri‐methylation is found to be upregulated and positively correlated with tumor progression and overall survival in CRC. This discovery suggests that SETDB1‐mediated tri‐methylation at K473 is a vital regulatory mechanism for lactate shuttle and tumor progression. Additionally, MCT1 K473 methylation may be a potential prognostic biomarker and promising therapeutic target for CRC.

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“…Moon et al showed that intermittent NBO alone or combined with carboplatin could be tumoricidal by induction of oxidative stress and apoptosis [ 62 ]. It has also been shown that, hyperoxia up to 60% O 2 increased lactate and intracellular acidification and significantly retarding tumor growth and metastasis in lung cancer [ 63 ]. In addition, Bels et al also examined hyperoxia up to 60% O 2 against hematopoietic lymphoid cancer cell lines and had adverse inhibitory effects on leukemia cell proliferation [ 64 ].…”

Section: Discussionmentioning

confidence: 99%

Comparison effects of Ferula gummosa essential oil and Beta-pinene Alginate nanoparticles on human melanoma and breast cancer cells proliferation and apoptotic index in short term normobaric hyperoxic model

Osanloo,

Pishamad,

ghanbariasad

et al. 2023

BMC Complement Med Ther

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Background Breast cancer is the most common cancer among women, and melanoma is the most dreadful type of skin cancer. Due to the side effects of chemotherapy drugs, the development of new herbal nano-medicines has been considered. Methods This study first investigated the chemical composition of Ferula gummosa essential oil using GC-MS analysis; β-pinene, with 61.57%, was the major compound. Next, alginate nanoparticles containing β-pinene and the essential oil with particle sizes of 174 ± 7 and 137 ± 6 nm were prepared. Meanwhile, their zeta potentials were 12.4 ± 0.7 and 28.1 ± 1 mV. Besides, the successful loading of β-pinene and the essential oil in nanoparticles was confirmed using ATR-FTIR analysis. After that, their effects on viability and apoptotic index of human melanoma and breast cancer cells were investigated in normoxia and normobaric hyperoxia (NBO) conditions. Results The best efficacy on A-375 and MDA-MB-231 cells was achieved by alginate nanoparticles containing the EO at hyperoxic and normoxia conditions; IC50 76 and 104 µg/mL. Besides, it affected apoptosis-involved genes; as Bax/Bcl-2 ratio was higher than 1, conditions for induction of apoptosis were obtained. Higher sensitivity was observed in the A-375 cell line treated with Alg-EO in the NBO model. Conclusions Alginate nanoparticles containing F. gummosa EO could be considered for further investigation in anticancer studies. Also, it may be expected that NBO can be a new strategy for delaying cancer progression and improving nanotherapy efficacy.

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Hyperoxia induces glucose metabolism reprogramming and intracellular acidification by suppressing MYC/MCT1 axis in lung cancer

Cited by 7 publications

References 41 publications

ENO2 promotes anoikis resistance in anaplastic thyroid cancer by maintaining redox homeostasis

ENO2 promotes anoikis resistance in anaplastic thyroid cancer by maintaining redox homeostasis

SETDB1 Methylates MCT1 Promoting Tumor Progression by Enhancing the Lactate Shuttle

Comparison effects of Ferula gummosa essential oil and Beta-pinene Alginate nanoparticles on human melanoma and breast cancer cells proliferation and apoptotic index in short term normobaric hyperoxic model

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