TWIST1 transcriptionally regulates glycolytic genes to promote the Warburg metabolism in pancreatic cancer

Wang, Xinxing; Yin, Guo-Qing; Zhang, Zhenhai; Rong, Zhonghou; Wang, Zhiyi; Du, Dongdong; Wang, Yadong; Gao, Ruxin; Xian, Guozhe

doi:10.1016/j.yexcr.2019.111713

Cited by 29 publications

(23 citation statements)

References 28 publications

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“…The number of invaded cells was counted in six randomly selected microscopic fields. [17]. In brief, total RNA was isolated from PDAC cells by using the Trizol reagent (Invitrogen, USA) and reverse transcribed were performed using the PrimeScript RT-PCR Kit (Takara, Japan).…”

Section: Cell Invasion Assaymentioning

confidence: 99%

GFAT1/HBP/O-GlcNAcylation Axis Regulatesβ-Catenin Activity to Promote Pancreatic Cancer Aggressiveness

Jia

et al. 2020

BioMed Research International

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Reprogrammed glucose and glutamine metabolism are essential for tumor initiation and development. As a branch of glucose and metabolism, the hexosamine biosynthesis pathway (HBP) generates uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) and contributes to the O-GlcNAcylation process. However, the spectrum of HBP-dependent tumors and the mechanisms by which the HBP promotes tumor aggressiveness remain areas of active investigation. In this study, we analyzed the activity of the HBP and its prognostic value across 33 types of human cancers. Increased HBP activity was observed in pancreatic ductal adenocarcinoma (PDAC), and higher HBP activity predicted a poor prognosis in PDAC patients. Genetic silencing or pharmacological inhibition of the first and rate-limiting enzyme of the HBP, glutamine:fructose-6-phosphate amidotransferase 1 (GFAT1), inhibited PDAC cell proliferation, invasive capacity, and triggered cell apoptosis. Notably, these effects can be restored by addition of UDP-GlcNAc. Moreover, similar antitumor effects were noticed by pharmacological inhibition of GFAT1 with 6-diazo-5-oxo-lnorleucine (DON) or Azaserine. PDAC is maintained by oncogenic Wnt/β-catenin transcriptional activity. Our data showed that GFAT1 can regulate β-catenin expression via modulation of the O-GlcNAcylation process. TOP/FOP-Flash and real-time qPCR analysis showed that GFAT1 knockdown inhibited β-catenin activity and the transcription of its downstream target genes CCND1 and MYC. Ectopic expression of a stabilized form of β-catenin restored the suppressive roles of GFAT1 knockdown on PDAC cell proliferation and invasion. Collectively, our findings indicate that higher GFAT1/HBP/O-GlcNAcylation exhibits tumor-promoting roles by maintaining β-catenin activity in PDAC.

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Section: Cell Invasion Assaymentioning

confidence: 99%

GFAT1/HBP/O-GlcNAcylation Axis Regulatesβ-Catenin Activity to Promote Pancreatic Cancer Aggressiveness

Jia

et al. 2020

BioMed Research International

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“…Of note, Twist1 is a regulator of aerobic glycolysis in PDAC. Using human pancreatic cancer cell lines, Twist1 has shown to transcriptionally regulate the expression of key glycolytic genes, such as GLUT1, HK2, ENO1, and PKM2 to promote the Warburg effect [60] . Whether TGIF1 functions to limit this pro-tumorigenic activity of Twist1 remains to be established.…”

Section: Functional Interaction Between Tgif1 and Twist1 In Pdacmentioning

confidence: 99%

TGIF1-Twist1 axis in pancreatic ductal adenocarcinoma

Atfi

2020

Computational and Structural Biotechnology Journal

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TG-interacting factor 1 (TGIF1) exerts inhibitory effects on transforming growth factor-beta (TGF-β) signaling by suppressing Smad signaling pathway at multiple levels. TGIF1 activity is important for normal embryogenesis and organogenesis, yet its dysregulation can culminate in tumorigenesis. For instance, increased expression of TGIF1 correlates with poor prognosis in triple-negative breast cancer patients, and enforced expression of TGIF1 facilitates Wnt-driven mammary tumorigenesis, suggesting that TGIF1 might function as an oncoprotein. Quite surprisingly, TGIF1 has recently been shown to function as a tumor suppressor in pancreatic ductal adenocarcinoma (PDAC), possibly owing to its ability to antagonize the pro-malignant transcription factor Twist1. In this article, we will briefly elaborate on the biological and clinical significance of the unique tumor-suppressive function of TGIF1 and its functional interaction with Twist1 in the context of PDAC pathogenesis and progression.

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“…[24][25][26][27] Pan et al reported that TWIST1 was selectively expressed in adipose tissue, and was recruited to suppress mitochondrial metabolism and uncoupling, maintaining the of energy homeostasis. [24] Furthermore, TWIST1 was also reported to take part in glucose metabolism [26] and mitochondrial oxidative metabolism. [27] Along with our findings from the Ensemble Browser (Fig.…”

Section: The Functions Of Ac0039863 Have Not Been Reported Interactmentioning

confidence: 99%

Identification of AC003986.3 as an independent risk factor for glioma patient survival and functional analysis

Liu

et al. 2020

Preprint

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Background To validate the potential of AC003986.3 in predicting glioma patient survival and analyze its underlying function and mechanism. Methods Gene expression and clinical features of the patients were obtained from The Cancer Genome Atlatls. Correlation between AC003986.3 expression profile and patient clinical features and survival were analyzed. Multivariate Cox regression was employed to determine the risk factors for patient survival and construct the prediction model for survival. Validation of the multivariate Cox regression model was tested by comparing the survival curves between the model-predicted high and low death risk subgroups and calculating the accuracy of predicting 1, 2, 3, and 5 years survival by the model. Target genes were predicted with Ensemble Browser. Gene set enrichment analysis was performed to explore AC003986.3 related gene sets enrichment in Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways. Results 655 samples with gene expression and complete clinical features were obtained from The Cancer Genome Atlas. Clinical features enrolled in this study were follow up time, survival status, race, gender, race and pathological grade. AC003986.3 expression was positively related to patient age and pathological grade. High AC003986.3 expression glioma patients suffered a poorer survival than those with low expression. Multivariate Cox regression revealed that AC003986.3 expression was an independent risk factor for patient survival irrespective of age and pathological grade. Predicted by Ensemble Browser, TWIST1 was the target of AC003986.3. Gene set enrichment analysis revealed that AC003986.3 related gene sets were mainly enriched in cell metabolism. Conclusions AC003986.3 expression is closely related to age and pathological grade in glioma patients, and is an independent risk factor for patient survival irrespective of age and pathological grade. AC003986.3 is mainly involved in regulating tumor cell metabolism, and this effect is probably mediated by TWIST1.

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TWIST1 transcriptionally regulates glycolytic genes to promote the Warburg metabolism in pancreatic cancer

Cited by 29 publications

References 28 publications

GFAT1/HBP/O-GlcNAcylation Axis Regulatesβ-Catenin Activity to Promote Pancreatic Cancer Aggressiveness

GFAT1/HBP/O-GlcNAcylation Axis Regulatesβ-Catenin Activity to Promote Pancreatic Cancer Aggressiveness

TGIF1-Twist1 axis in pancreatic ductal adenocarcinoma

Identification of AC003986.3 as an independent risk factor for glioma patient survival and functional analysis

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