Targeting PFKL with penfluridol inhibits glycolysis and suppresses esophageal cancer tumorigenesis in an AMPK/FOXO3a/BIM-dependent manner

Zheng, Can‐Can; Yu, Xiaomei; Liang, Yiyao; Zhu, Yifei; He, Yan; Liao, Long; Wang, Ding-Kang; Yang, Yanming; Yin, Xinhua; Li, Ang; He, Qing‐Yu; Li, Bin

doi:10.1016/j.apsb.2021.09.007

Cited by 51 publications

(34 citation statements)

References 50 publications

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“…Many linear and cyclic alcohols (25-37) performed as suitable reactants (Scheme 1). Readily available tertiary (1-10, 23, 24), secondary (11)(12)(13)(14)(15)(16)(17)(18)(19), and primary alcohols (20)(21)(22) were all tested. To our delight, all the studied alcohols showed satisfactory reactivities, resulting in moderate to outstanding isolated yields of the products.…”

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confidence: 99%

“…8–10 Radical tactics were also applied to transform C–C bonds, which have been extended to unstrained cyclic amines and alcohols lately. 3 a , b ,11 Hydroxyl groups are extensively present in natural products, 12 pharmaceuticals, 13 bioactive compounds, 14 and chemical feedstock compounds, 15 and can be easily transformed from alkenes, halides, ketones, aldehydes, esters, etc . 16 Thus, a method for editing various C–C bonds adjacent to hydroxyl groups can offer a bridge for deconstructive diversification in operationally simple ways.…”

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confidence: 99%

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Iron-catalyzed deconstructive alkylation through chlorine radical induced C–C single bond cleavage under visible light

Liu

Wang

et al. 2022

Chem. Commun.

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confidence: 99%

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confidence: 99%

Iron-catalyzed deconstructive alkylation through chlorine radical induced C–C single bond cleavage under visible light

Liu

Wang

et al. 2022

Chem. Commun.

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“…The production of lactate constitutes a local acidic environment for tumor cell proliferation and activates the cascade reaction of protein hydrolases to convert pre-matrix metalloproteinases into matrix metalloproteinases, which promote the degradation of the extracellular matrix of cancer cells and facilitate the invasion of surrounding tissues by tumor cells ( 38 ). A number of cancers have been identified to have PFKL as a component of the glycolysis process, including lung cancer ( 39 ), esophageal cancer ( 40 ), neuroblastoma ( 41 ) and hepatocellular carcinoma ( 42 ). The Bcl-2 protein family is one of the core regulatory mechanisms of apoptosis, which can receive and transmit intrinsic intracellular signals or external environmental stress signals, such as nutrient or hypoxic stress, DNA damage, oncogene over-activation, endoplasmic reticulum stress, etc ( 43 ).…”

Section: Discussionmentioning

confidence: 99%

Development and Validation of a 6-Gene Hypoxia-Related Prognostic Signature For Cholangiocarcinoma

Sun

Wang²,

Xiao

et al. 2022

Front. Oncol.

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Cholangiocarcinoma (CHOL) is highly malignant and has a poor prognosis. This study is committed to creating a new prognostic model based on hypoxia related genes. Here, we established a novel tumor hypoxia-related prognostic model consisting of 6 hypoxia-related genes by univariate Cox regression and the least absolute shrinkage and selection operator (LASSO) algorithm to predict CHOL prognosis and then the risk score for each patient was calculated. The results showed that the patients with high-risk scores had poor prognosis compared with those with low-risk scores, which was verified as an independent predictor by multivariate analysis. The hypoxia-related prognostic model was validated in both TCGA and GEO cohorts and exhibited excellent performance in predicting overall survival in CHOL. The PPI results suggested that hypoxia-related genes involved in the model may play a central role in regulating the hypoxic state. In addition, the presence of IDH1 mutations in the high-risk group was high, and GSEA results showed that some metabolic pathways were upregulated, but immune response processes were generally downregulated. These factors may be potential reasons for the high-risk group with worse prognosis. The analysis of different immune regulation-related processes in the high- and low-risk groups revealed that the expression of genes related to immune checkpoints would show differences between these two groups. We further verified the expression of the oncogene PPFIA4 in the model, and found that compared with normal samples, CHOL patients were generally highly expressed, and the patients with high-expression of PPFIA4 had a poor prognosis. In summary, the present study may provide a valid prognostic model for bile duct cancer to inform better clinical management of patients.

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“…Although many new therapeutic and diagnostic methods have been introduced, disease recurrence rates remain high, prognosis remains poor, and there still is no curative treatment. In addition, research into the treatment of ESCC has revealed a number of potential therapeutic targets such as orai1-mediated calcium signaling and PFKL (phosphate kinase, live type), however, further research is still needed (Zhu et al., 2014 ; Cui et al., 2018 ; Zheng et al., 2022 ).…”

Section: Discussionmentioning

confidence: 99%

A recombinant scFv antibody-based fusion protein that targets EGFR associated with IMPDH2 downregulation and its drug conjugate show therapeutic efficacy against esophageal cancer

Zhao

Tao

et al. 2022

Drug Delivery

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The present study aimed to evaluate the anti-tumor efficacy of the epidermal growth factor receptor (EGFR)-targeting recombinant fusion protein Fv-LDP-D3 and its antibody-drug conjugate Fv-LDP-D3-AE against esophageal cancer. Fv-LDP-D3, consisting of the fragment variable (Fv) of an anti-EGFR antibody, the apoprotein of lidamycin (LDP), and the third domain of human serum albumin (D3), exhibited a high binding affinity for EGFR-overexpressing esophageal cancer cells, inhibited EGFR phosphorylation and down-regulated inosine monophosphate dehydrogenase type II (IMPDH2) expression. Fv-LDP-D3 was taken up by cancer cells through intensive macropinocytosis; it inhibited the proliferation and induced the apoptosis of esophageal cancer cells. In vivo imaging revealed that Fv-LDP-D3 displayed specific tumor-site accumulation and a long-lasting retention over a 26-day period. Furthermore, Fv-LDP-D3-AE, a pertinent antibody-drug conjugate prepared by integrating the enediyne chromophore of lidamycin into the Fv-LDP-D3 molecule, displayed highly potent cytotoxicity, inhibited migration and invasion, induced apoptosis and DNA damage, arrested cells at G2/M phase, and caused mitochondrial damage in esophageal cancer cells. More importantly, both of Fv-LDP-D3 and Fv-LDP-D3-AE markedly inhibited the growth of esophageal cancer xenografts in athymic mice at well tolerated doses. The present results indicate that Fv-LDP-D3, and Fv-LDP-D3-AE exert prominent antitumor efficacy associated with targeting EGFR, suggesting their potential as promising candidates for targeted therapy against esophageal cancer.

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Targeting PFKL with penfluridol inhibits glycolysis and suppresses esophageal cancer tumorigenesis in an AMPK/FOXO3a/BIM-dependent manner

Cited by 51 publications

References 50 publications

Iron-catalyzed deconstructive alkylation through chlorine radical induced C–C single bond cleavage under visible light

Iron-catalyzed deconstructive alkylation through chlorine radical induced C–C single bond cleavage under visible light

Development and Validation of a 6-Gene Hypoxia-Related Prognostic Signature For Cholangiocarcinoma

A recombinant scFv antibody-based fusion protein that targets EGFR associated with IMPDH2 downregulation and its drug conjugate show therapeutic efficacy against esophageal cancer

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