Thymidine phosphorylase promotes malignant progression in hepatocellular carcinoma through pentose Warburg effect

Zhang, Qiang; Qin, Yuan; Zhao, Jianmin; Tang, Yanting; Hu, Xuejiao; Zhong, Weilong; Li, Mimi; Zong, Shumin; Li, Meng; Tao, Honglian; Zhang, Zhen; Chen, Shuang; Liu, Huijuan; Yang, Lan; Zhou, Honggang; Liu, Yanrong; Sun, Tao; Yang, Cheng

doi:10.1038/s41419-018-1282-6

Cited by 21 publications

(15 citation statements)

References 39 publications

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“…Bioinformatics analysis allows the identification of tumor-associated node genes from large data repositories to assist in the clarification of mechanisms and the prognostic assessment of cancer [ 15 , 22 ]. In the present study, we chose 9 samples of circulating NSCLC tumor cells and 9 samples of nonmetastatic NSCLC tumor cells in a GEO database to identify DEGs.…”

Section: Discussionmentioning

confidence: 99%

“…In the present study, the GEO database of GSE50991 containing mRNA expression profiles of circulating and non-metastatic lung tumor cells was used [ 14 ]. By investigating differential gene expression and function and conducting signaling pathway enrichment analyses [ 15 ], we identified TPX2 as the key regulatory gene in NSCLC metastasis and malignant progression. TPX2 overexpression has been found in a wide range of tumor types, including bladder, cervical, gastric, and hepatocellular carcinoma cancers [ 16 – 19 ].…”

Section: Introductionmentioning

confidence: 99%

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TPX2 Promotes Metastasis and Serves as a Marker of Poor Prognosis in Non-Small Cell Lung Cancer

Zhou

Wang

Aibaidula³

et al. 2020

Med Sci Monit

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Background Metastasis contributes to the high mortality rate of non-small cell lung cancer (NSCLC), and gaining a better understanding of its metastatic mechanisms would aid in initiating effective clinical treatment. Material/Method In this study, bioinformatics analyses of the GEO database and TCGA-LUAD were first used to identify the key node gene regulating NSCLC malignant progression. Further in vitro experiments, including wound healing assay, invasion assay, Western blot assay, and luciferase report assay, were used to clarify the functions and mechanism of TPX2 in NSCLC. Results Results of the TCGA analysis showed that TPX2 was significantly positively correlated with tumor metastasis and growth and the clinical stage of NSCLC. In addition, high levels of TPX2 significantly indicated a poor survival rate. In vitro experimental results also revealed that the upregulation of TPX2 significantly promoted NSCLC cell migration and invasion and could affect cell replasticity. Further results indicated that TPX2 significantly activated the epithelial-mesenchymal transition process and promoted the expression and activities of matrix metalloproteinase (MMP)2 and MMP9. Conclusions This study demonstrated that TPX2 promotes the metastasis and malignant progression of NSCLC and could thus serve as a marker of poor prognosis in NSCLC.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

TPX2 Promotes Metastasis and Serves as a Marker of Poor Prognosis in Non-Small Cell Lung Cancer

Zhou

Wang

Aibaidula³

et al. 2020

Med Sci Monit

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“…Cellular metabolisms related to ATP production in malignant cells are more active than normal cells 18 . HCC cells have exaggerated glucose uptake capability for their intensive anaerobic glycolysis which provides them enough energy to survive in harsh tumor microenvironment 19,20 . The chemoresistance of HCC cells closely correlates to the cellular metabolism; through the overwhelming anaerobic glycolytic activity, the accommodation of metabolites and the enhanced epithelial–mesenchymal transition (EMT) afterward take place 21,22 .…”

Section: Introductionmentioning

confidence: 99%

SREBP-1 inhibitor Betulin enhances the antitumor effect of Sorafenib on hepatocellular carcinoma via restricting cellular glycolytic activity

et al. 2019

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Lipid metabolism that correlates tightly to the glucose metabolic regulation in malignant cells includes hepatocellular carcinoma (HCC) cells. The transcription factor Sterol Regulatory Element Binding Protein 1 (SREBP-1), a regulator of fatty acid synthesis, has been shown to pivotally regulate the proliferation and metastasis of HCC cells. However, the intrinsic mechanism by which SREBP-1 regulates the survival of HCC cells remains unclear. In this study, among HCC patients who had dismal responses to Sorafenib, a high SREBP-1 level was found in the tumors and correlated to poor survival. This observation suggested the negative role of SREBP-1 in clinical HCC prognosis. Our mechanistical studies reveal that the inhibition of SREBP-1 via its inhibitor Betulin suppresses cellular glucose metabolism. In addition to the reduced glycolytic activity, a thwarted metastatic potential was observed in HCC cells upon Betulin administration. Moreover, our data show that SREBP-1 inhibition facilitated the antitumor effects of Sorafenib on HCC cells and xenograft tumors.

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“…Structural features of VM were first reported by Maniotis et al in 1999 as a phenomenon wherein aggressive tumor cells mimic vascular endothelial cells to form embryonic vasculogenic networks enriched in extracellular matrix (ECM) components, through which blood cells can be transported 7 . VM occurs in numerous solid tumors, including melanoma, head and neck carcinoma, breast cancer, and hepatocellular carcinoma [8][9][10][11][12] . We previously reported VM in glioma in 2005 13 .…”

Section: Introductionmentioning

confidence: 99%

Tenascin-c mediated vasculogenic mimicry formation via regulation of MMP2/MMP9 in glioma

Cai

Wang

et al. 2019

Cell Death Dis

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Vasculogenic mimicry (VM), the formation of vessel-like structures by highly invasive tumor cells, has been considered one of several mechanisms responsible for the failure of anti-angiogenesis therapy in glioma patients. Therefore, inhibiting VM formation might be an effective therapeutic method to antagonize the angiogenesis resistance. This study aimed to show that an extracellular protein called Tenascin-c (TNC) is involved in VM formation and that TNC knockdown inhibits VM in glioma. TNC was upregulated with an increase in glioma grade. TNC and VM formation are potential independent predictors of survival of glioma patients. TNC upregulation was correlated with VM formation, and exogenous TNC stimulated VM formation. Furthermore, TNC knockdown significantly suppressed VM formation and proliferation in glioma cells in vitro and in vivo, with a reduction in cellular invasiveness and migration. Mechanistically, TNC knockdown decreased Akt phosphorylation at Ser 473 and Thr 308 and subsequently downregulated matrix metalloproteinase 2 and 9, both of which are important proteins associated with VM formation and migration. Our results indicate that TNC plays an important role in VM formation in glioma, suggesting that TNC is a potential therapeutic target for anti-angiogenesis therapy for glioma.

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Thymidine phosphorylase promotes malignant progression in hepatocellular carcinoma through pentose Warburg effect

Cited by 21 publications

References 39 publications

TPX2 Promotes Metastasis and Serves as a Marker of Poor Prognosis in Non-Small Cell Lung Cancer

TPX2 Promotes Metastasis and Serves as a Marker of Poor Prognosis in Non-Small Cell Lung Cancer

SREBP-1 inhibitor Betulin enhances the antitumor effect of Sorafenib on hepatocellular carcinoma via restricting cellular glycolytic activity

Tenascin-c mediated vasculogenic mimicry formation via regulation of MMP2/MMP9 in glioma

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