Notch signaling regulates the expression of glycolysis-related genes in a context-dependent manner during embryonic development

Kuwabara, S.; Yamaki, Misato; Yu, Hai; Itoh, Motoyuki

doi:10.1016/j.bbrc.2018.06.079

Cited by 19 publications

(20 citation statements)

References 31 publications

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“…This is consistent with the idea that quiescent MuSCs mainly depend on low-level fatty acid-driven oxidative phosphorylation (OXPHOS) (Pala et al, 2018). Notch signaling is highly context dependent and promotes glycolysis, for example, in hematopoietic stem cells or breast cancer cells (Ciofani and Zuniga-Pflucker, 2005;Landor et al, 2011) or represses glucose metabolism, for example, in the developing nervous system (Kuwabara et al, 2018) or mesenchymal stem cells (Lee and Long, 2018). Treatment of WT juvenile MPs with a Notch ligand strongly inhibits glycolytic gene expression and to a milder extent OXPHOS gene expression, indicating a direct role of Notch signaling in metabolic quiescence induction in MPs.…”

Section: Metabolic Reprogramming In Juvenile Mps Quiescence Induction Kegg Analysis Of Nf1supporting

confidence: 88%

Neurofibromin 1 controls metabolic balance and Notch-dependent quiescence of juvenile myogenic progenitors

Wei

Lienhard

Murgai

et al. 2021

Preprint

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Patients affected by neurofibromatosis type 1 (NF1) frequently show muscle weakness with unknown etiology. Here we show that Neurofibromin-1 (Nf1) is not required in muscle fibers, but specifically in early postnatal myogenic progenitors (MPs), where Nf1 loss led to cell cycle exit and differentiation blockade, depleting the MP pool resulting in reduced myonuclear accrual as well as reduced muscle stem cell numbers. This was caused by precocious induction of stem cell quiescence coupled to metabolic reprogramming of MPs impinging on glycolytic shutdown, which was conserved in muscle fibers. We show that a Mek/Erk/NOS pathway hypersensitizes Nf1-deficient MPs to Notch signaling, consequently, early postnatal Notch pathway inhibition ameliorated premature quiescence, metabolic reprogramming and muscle growth. This reveals an unexpected role of Ras/Mek/Erk signaling supporting postnatal MP quiescence in concert with Notch signaling, which is controlled by Nf1 safeguarding coordinated muscle growth and muscle stem cell pool establishment. Furthermore, our data suggest transmission of metabolic reprogramming across cellular differentiation, affecting fiber metabolism and function in NF1.

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Section: Metabolic Reprogramming In Juvenile Mps Quiescence Induction Kegg Analysis Of Nf1supporting

confidence: 88%

Neurofibromin 1 controls metabolic balance and Notch-dependent quiescence of juvenile myogenic progenitors

Wei

Lienhard

Murgai

et al. 2021

Preprint

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“…Several transcriptional factors that have been reported to regulate glycolysiscyclic AMP (cAMP)-responsive element-binding protein (CREB), TEA domain transcription factor 1 (TEAD1), GLI family zinc finger 1 (GLI1), and transcription factor (TCF)/lymphoid enhancer binding factor 1 (LEF1)-were studied by luciferase reporter assays. [19][20][21][22][23] We found that transfection of LINC00941 markedly increased the transcriptional activity of TEAD1 but not the other transcription factors in PANC-1 cells (Figure 5A), and knockdown of LINC00941 reduced the transcriptional activity of TEAD 1 (Figure S3), indicating that the Hippo pathway may mediate the regulation of glycolysis by LINC00941. Thus, we detected the expression of three typical downstream genes of the Hippo pathway: CTGF, CYR61, and ANKRD1.…”

Section: Linc00941 Activates the Hippo Pathway To Enhance Glycolysis In Pdac Cellsmentioning

confidence: 95%

LINC00941 promotes glycolysis in pancreatic cancer by modulating the Hippo pathway

Cui

et al. 2021

Molecular Therapy - Nucleic Acids

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Pancreatic ductal adenocarcinoma (PDAC) is one of most lethal cancers and is projected to be the second leading cause of cancer deaths in the United States by 2030. The lack of effective treatment and increased incidence in PDAC encourage a deeper knowledge of PDAC progression. By analyzing a long noncoding RNA (lncRNA) dataset, we found that increased LINC00941 expression led to poor outcomes in PDAC patients. Furthermore, in vitro and in vivo experiments revealed that LINC00941 promoted PDAC cancer cell growth by enhancing aerobic glycolysis. Mechanistically, LINC00941 was found to interact with mammalian STE20-like protein kinase 1 (MST1), which facilitated the protein phosphatase 2A (PP2A)-mediated dephosphorylation of MST1, resulting in Hippo pathway activation and consequently, enhanced glycolysis in PDAC. These results suggest that LINC00941 plays a key role in regulating PDAC tumorigenesis, potentially highlighting novel avenues for PDAC therapy.

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“…Our data show that Notch1 regulates Notch1 knockdown lung cancer cells regulates glycolytic gene expression, glucose uptake, and the level of lactate, a metabolite that can facilitate tumor growth, indicating that Notch1 is a key transcription factor for the regulation of aerobic glycolysis. Notch1 signaling increases the rate of glycolysis through the upregulation of glycolysis-related gene expressions such as GLUT1 and GLUT3 [ 27 , 28 ]. The function of Notch1 in glycolysis in lung adenocarcinoma at least partly explains the inhibited expression of glycolytic genes induced by Notch1 knockdown.…”

Section: Discussionmentioning

confidence: 99%

Notch1/TAZ axis promotes aerobic glycolysis and immune escape in lung cancer

Xie

Jiang

2021

Cell Death Dis

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Oncogenic signaling pathway reprograms cancer cell metabolism to promote aerobic glycolysis in favor of tumor growth. The ability of cancer cells to evade immunosurveillance and the role of metabolic regulators in T-cell functions suggest that oncogene-induced metabolic reprogramming may be linked to immune escape. Notch1 signaling, dysregulated in lung cancer, is correlated with increased glycolysis. Herein, we demonstrate in lung cancer that Notch1 promotes glycolytic gene expression through functional interaction with histone acetyltransferases p300 and pCAF. Notch1 signaling forms a positive feedback loop with TAZ. Notch1 transcriptional activity was increased in the presence of TAZ and the activation was TEAD1 independent. Notably, aerobic glycolysis was critical for Notch1/TAZ axis modulation of lung cancer growth in vitro and in vivo. Increased level of extracellular lactate via Notch1/TAZ axis inhibited cytotoxic T-cell activity, leading to the invasive characteristic of lung cancer cells. Interaction between Notch1 and TAZ promoted aerobic glycolysis and immune escape in lung cancer. Our findings provide potential therapeutic targets against Notch1 and TAZ and would be important for clinical translation in lung cancer.

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Notch signaling regulates the expression of glycolysis-related genes in a context-dependent manner during embryonic development

Cited by 19 publications

References 31 publications

Neurofibromin 1 controls metabolic balance and Notch-dependent quiescence of juvenile myogenic progenitors

Neurofibromin 1 controls metabolic balance and Notch-dependent quiescence of juvenile myogenic progenitors

LINC00941 promotes glycolysis in pancreatic cancer by modulating the Hippo pathway

Notch1/TAZ axis promotes aerobic glycolysis and immune escape in lung cancer

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