Bittersweet tumor development and progression: Emerging roles of epithelial plasticity glycosylations

Phillips, Ryan; C, Lam; Wang, Hailun; Tran, Phuoc T.

doi:10.1016/bs.acr.2019.01.002

Cited by 12 publications

(8 citation statements)

References 94 publications

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“…In addition, the combination treatment of DON and palbociclib promoted a CAF-like morphology in cocultured TAFs which in turn appears to reduce EMT in the HCC827. This aligns with previous studies where altering protein glycosylation mediated many cellular changes associated with EMT and cell-cell adhesion (21,53).…”

Section: Discussionsupporting

confidence: 92%

“…O-linked glycosylation has been associated with several cancer hallmarks (20,21). However, very little is known about: 1) which proteins are O-glycosylated 2) the effect(s) of O-glycosylation on protein function, and 3) how protein O-glycosylation impacts cell-cell crosstalk.…”

Section: Introductionmentioning

confidence: 99%

“…While previous results on CAFs assessed metabolic reprogramming toward HBP in the tumor stroma, direct measurements of the O-glycoproteome changes following tumor-stroma interactions using a multi-modal approach have yet to be reported. O-linked glycosylation has been associated with several cancer hallmarks (20,21). However, very little is known about: 1) which proteins are O-glycosylated 2) the effect(s) of Oglycosylation on protein function, and 3) how protein O-glycosylation impacts cell-cell crosstalk.…”

Section: Introductionmentioning

confidence: 99%

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Multi-Omics Analysis of Fibroblasts from the Invasive Tumor Edge Reveals that Tumor-Stroma Crosstalk Induces O-glycosylation of the CDK4-pRB Axis

Bouchard

Fjg²,

et al. 2021

Preprint

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The invasive leading edge represents a potential gateway for tumor invasion. We hypothesize that crosstalk between tumor and stromal cells within the tumor microenvironment (TME) results in the activation of key biological pathways depending on their location in the tumor (edge vs core). Here, we highlight phenotypic differences between Tumor-Adjacent-Fibroblasts (TAFs) from the invasive edge and Cancer-Associated Fibroblasts (CAFs) from the tumor core, established from human lung adenocarcinomas. We use an innovative multi-omics approach that includes genomics, proteomics and, O-glycoproteomics to characterize crosstalk between TAFs and cancer cells. Our analysis shows that O-glycosylation, an essential post-translational modification resulting from sugar metabolism, alters key biological pathways including the CDK4-pRB axis in the stroma, and indirectly modulates pro-invasive features of cancer cells. In summary, aside from improving the efficacy of CDK4 inhibitors anti-cancer agents, the O-glycoproteome poses a new consideration for important biological processes involved in tumor-stroma crosstalk.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Multi-Omics Analysis of Fibroblasts from the Invasive Tumor Edge Reveals that Tumor-Stroma Crosstalk Induces O-glycosylation of the CDK4-pRB Axis

Bouchard

Fjg²,

et al. 2021

Preprint

View full text Add to dashboard Cite

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“…However, fatty acid oxidation (FAO) was unchanged in IAV-infected DC concomitant to a decrease in intracellular free fatty acids (Fig 2E & 2F). Together, the increase in glycolysis and glutaminolyisis with decreased pyruvate utilization in the TCA cycle is consistent with the two major metabolic pathways becoming uncoupled to maintain ATP production while increasing metabolic plasticity [31][32][33][34][35][36].…”

Section: Restructure Metabolic Flux After Iav Infectionsupporting

confidence: 56%

Dynamic metabolic reprogramming in dendritic cells: An early response to influenza infection that is essential for effector function

et al. 2020

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Infection with the influenza virus triggers an innate immune response that initiates the adaptive response to halt viral replication and spread. However, the metabolic response fueling the molecular mechanisms underlying changes in innate immune cell homeostasis remain undefined. Although influenza increases parasitized cell metabolism, it does not productively replicate in dendritic cells. To dissect these mechanisms, we compared the metabolism of dendritic cells to that of those infected with active and inactive influenza A virus and those treated with toll-like receptor agonists. Using quantitative mass spectrometry, pulse chase substrate utilization assays and metabolic flux measurements, we found global metabolic changes in dendritic cells 17 hours post infection, including significant changes in carbon commitment via glycolysis and glutaminolysis, as well as mitochondrial respiration. Influenza infection of dendritic cells led to a metabolic phenotype distinct from that induced by TLR agonists, with significant resilience in terms of metabolic plasticity. We identified c-Myc as one transcription factor modulating this response. Restriction of c-Myc activity or mitochondrial substrates significantly changed the immune functions of dendritic cells, such as reducing motility and T cell activation. Transcriptome analysis of inflammatory dendritic cells isolated following influenza infection showed similar metabolic reprogramming occurs in vivo. Thus, early in the infection process, dendritic cells respond with global metabolic restructuring, that is present in inflammatory lung dendritic cells after infection, and this is important for effector function. These findings suggest metabolic switching in dendritic cells plays a vital role in initiating the immune response to influenza infection.

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“…Glucose transporters, especially GLUT-1 and GLUT-3, promote tumor progression by increasing glucose influx and activating downstream molecular pathways (38). GLUT-1 increases matrix metalloproteinase 2 (MMP-2) in vitro and in vivo, which contributes to EMT and cellular invasiveness (34,39). GLUT-3 gene could be activated by ZEB1, which is an EMT marker (34).…”

Section: Glucose Metabolism and Emtmentioning

confidence: 99%

Glucose Metabolism on Tumor Plasticity, Diagnosis, and Treatment

et al. 2020

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Malignant cells support tumor proliferation and progression by adopting to metabolic changes. Tumor cells altered metabolism by increasing glucose uptake and fermentation of glucose to lactate, even in the aerobic state and the presence of functioning mitochondria. Glucose metabolism in tumor plasticity has attracted great interests by clinicians and scientists in the past decades. This review discusses the previous and emerging researches on the tumor plasticity altered by changing glucose metabolism in different cancer cells, including cancer stem cells (CSCs). In addition, we summarize the rising applications of glucose metabolism in tumor diagnosis and treatment. Our objective is to direct future investigation on this altered metabolic phenotype and its application in patient care.

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Bittersweet tumor development and progression: Emerging roles of epithelial plasticity glycosylations

Cited by 12 publications

References 94 publications

Multi-Omics Analysis of Fibroblasts from the Invasive Tumor Edge Reveals that Tumor-Stroma Crosstalk Induces O-glycosylation of the CDK4-pRB Axis

Multi-Omics Analysis of Fibroblasts from the Invasive Tumor Edge Reveals that Tumor-Stroma Crosstalk Induces O-glycosylation of the CDK4-pRB Axis

Dynamic metabolic reprogramming in dendritic cells: An early response to influenza infection that is essential for effector function

Glucose Metabolism on Tumor Plasticity, Diagnosis, and Treatment

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