Aldolase B Overexpression is Associated with Poor Prognosis and Promotes Tumor Progression by Epithelial-Mesenchymal Transition in Colorectal Adenocarcinoma

Li, Qingguo; Li, Yaqi; Xu, Junyan; Wang, Sheng; Xu, Ye; Li, Xinxiang; Cai, Sanjun

doi:10.1159/000477484

Cited by 65 publications

(66 citation statements)

References 26 publications

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“…This again indicates a critical metabolic change, as previously observed in chRCC (27) and in gastric cancer (35). Conversely, an over-expression of gluconeogenic genes and proteins is frequently found in other tumor species, such as the over-expression of ALDOB in ccRCC (36) and colon cancer (37)(38)(39), which was also associated with tumor progression and poor prognosis.…”

Section: Discussionsupporting

confidence: 74%

Papillary renal cell carcinomas rewire glutathione metabolism and are deficient in anabolic glucose synthesis

Alahmad

Paffrath

Clima

et al. 2019

Preprint

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Papillary renal cell carcinoma (pRCC) is a malignant kidney cancer with a prevalence of 7-20% of all renal tumors. Proteome and metabolome profiles of 19 pRCC and patient-matched healthy kidney controls were used to elucidate the regulation of metabolic pathways and the underlying molecular mechanisms. Glutathione (GSH), a main reactive oxygen species (ROS) scavenger, was highly increased and can be regarded as a new hallmark in this malignancy. Isotope tracing of pRCC derived cell lines revealed an increased de novo synthesis rate of GSH, based on glutamine consumption. Furthermore, rewiring of the main pathways involved in ATP and glucose synthesis was observed at the protein level. In contrast, transcripts encoding for the respiratory chain were not regulated, which prompts for non-genetic profiling. The molecular characteristics of pRCC are increased GSH synthesis to cope with ROS stress, deficient anabolic glucose synthesis, and compromised oxidative phosphorylation, which could potentially be exploited in innovative anti-cancer strategies.

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Section: Discussionsupporting

confidence: 74%

Papillary renal cell carcinomas rewire glutathione metabolism and are deficient in anabolic glucose synthesis

Alahmad

Paffrath

Clima

et al. 2019

Preprint

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“…Staining was performed as previously described. 30 Commercial monoclonal antibodies to KLF8 and GLUT4 were used as primary antibodies and PBS was used as a negative control. Evaluation of the results was performed according the criteria as recommended by the manufacturer.…”

Section: Ihc Stainingmentioning

confidence: 99%

KLF8 is associated with poor prognosis and regulates glycolysis by targeting GLUT4 in gastric cancer

Mao

Zhou

Liu

et al. 2019

J Cellular Molecular Medi

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Krüppel‐like transcription factor (KLF) family is involved in tumorigenesis in different types of cancer. However, the importance of KLF family in gastric cancer is unclear. Here, we examined KLF gene expression in five paired liver metastases and primary gastric cancer tissues by RT‐PCR, and immunohistochemistry was used to study KLF8 expression in 206 gastric cancer samples. The impact of KLF8 expression on glycolysis, an altered energy metabolism that characterizes cancer cells, was evaluated. KLF8 showed the highest up‐regulation in liver metastases compared with primary tumours among all KLF members. Higher KLF8 expression associated with larger tumour size ( P < 0.001), advanced T stage ( P = 0.003) and N stage ( P < 0.001). High KLF8 expression implied shorter survival outcome in both TCGA and validation cohort ( P < 0.05). Silencing KLF8 expression impaired the glycolysis rate of gastric cancer cells in vitro. Moreover, high KLF8 expression positively associated with SUVmax in patient samples. KLF8 activated the GLUT4 promoter activity in a dose‐dependent manner ( P < 0.05). Importantly, KLF8 and GLUT4 showed consistent expression patterns in gastric cancer tissues. These findings suggest that KLF8 modulates glycolysis by targeting GLUT4 and could serve as a novel biomarker for survival and potential therapeutic target in gastric cancer.

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“…A feature of this phenomenon, called the Warburg effect or aerobic glycolysis, is increased lactate production even at normal oxygen concentrations. Many glucose metabolic enzymes are unregulated or downregulated in cancer tissues, and have been validated as multifaceted enzymes that are involved in various processes in cancer metastases and progression [9][10][11][12].…”

Section: Introductionmentioning

confidence: 99%

PGK1 is a Potential Survival Biomarker and Invasion Promoter by Regulating the HIF-1α–Mediated Epithelial-Mesenchymal Transition Process in Breast Cancer

Wei

et al. 2018

Cell Physiol Biochem

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Background/Aims: Glycolysis, a multi-step enzymatic reaction, is considered to be the root of cancer development and progression. The aim of this study is to figure out which glycolysis enzyme participates in the progression of breast cancer and its possible mechanisms. Materials: We firstly screened out PGK1 by performing an RT-PCR array of glycolysis-related genes in three paired breast cancer samples, and further investigated PGK1 using TCGA and our own database. The effect and mechanism of PGK1 on cell invasion was further explored both in vitro and using patient samples. Results: PGK1 was most upregulated in T3N0 with distant metastases compared to those with no metastases. In the TCGA database, high PGK1 expression predicted poor overall survival (OS) in breast cancer and some other cancers (P< 0.001). In the validation cohort, high PGK1 expression was significantly correlated with larger tumor size (P=0.011) and advanced TNM stage (P=0.033), and PGK1 expression was an independent prognostic factor for OS and disease free survival (DFS) in both univariate and multivariate regression analyses (P< 0.05). Functional studies indicated that knockdown of PGK1 expression significantly inhibited invasion and reversed the epithelial-mesenchymal transition process in breast cancer cells (P< 0.05). Mechanistically, PGK1 increased HRE luciferase activity in a dose-dependent manner, while silencing PGK1 expression decreased HRE activity. Conclusion: High PGK1 expression was associated with poor prognosis in breast cancer, because PGK1 and HIF-1α formed a positive feed-forward loop and thus stimulated breast cancer progression and metastases. Based on these results, PGK1 may serve as a promising biomarker and target therapy for breast cancer.

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Aldolase B Overexpression is Associated with Poor Prognosis and Promotes Tumor Progression by Epithelial-Mesenchymal Transition in Colorectal Adenocarcinoma

Cited by 65 publications

References 26 publications

Papillary renal cell carcinomas rewire glutathione metabolism and are deficient in anabolic glucose synthesis

Papillary renal cell carcinomas rewire glutathione metabolism and are deficient in anabolic glucose synthesis

KLF8 is associated with poor prognosis and regulates glycolysis by targeting GLUT4 in gastric cancer

PGK1 is a Potential Survival Biomarker and Invasion Promoter by Regulating the HIF-1α–Mediated Epithelial-Mesenchymal Transition Process in Breast Cancer

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