Nutrient stress revamps cancer cell metabolism

Moscat, Jorge; Richardson, Adam D.; Diaz-Meco, Marı́a T.

doi:10.1038/cr.2015.38

Cited by 6 publications

(4 citation statements)

References 10 publications

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“…Furthermore, results from Dejure and colleagues showed glutamine deprivation only halted the proliferation of colon cancer cells, but not killed them (11). Notably, nutrient deprivation has been correlated with poor patient survival, suggesting that instead of killing the tumor, the scarcity of nutrients can make the cancer cell stronger (12). Therefore, it is crucial to investigate the mechanisms that are required to accommodate nutrient stresses as an alternative strategy for the therapeutic treatment of pancreatic cancer.…”

Section: Introductionmentioning

confidence: 99%

Nutrient Stress–Dysregulated Antisense lncRNA GLS-AS Impairs GLS-Mediated Metabolism and Represses Pancreatic Cancer Progression

et al. 2019

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Cancer cells are known to undergo metabolic reprogramming, such as glycolysis and glutamine addiction, to sustain rapid proliferation and metastasis. It remains undefined whether long noncoding RNAs (lncRNA) coordinate the metabolic switch in pancreatic cancer. Here we identify a nuclear-enriched antisense lncRNA of glutaminase (GLS-AS) as a critical regulator involved in pancreatic cancer metabolism. GLS-AS was downregulated in pancreatic cancer tissues compared with noncancerous peritumor tissues. Depletion of GLS-AS promoted proliferation and invasion of pancreatic cancer cells both in vitro and in xenograft tumors of nude mice. GLS-AS inhibited GLS expression at the posttranscriptional level via formation of double stranded RNA with GLS pre-mRNA through ADAR/Dicer-dependent RNA interference. GLS-AS expression was transcriptionally downregulated by nutrient stress-induced Myc. Conversely, GLS-AS decreased Myc expression by impairing the GLS-mediated stability of Myc protein. These results imply a reciprocal feedback loop wherein Myc and GLS-AS regulate GLS overexpression during nutrient stress. Ectopic overexpression of GLS-AS inhibited proliferation and invasion of pancreatic cancer cells by repressing the Myc/GLS pathway. Moreover, expression of GLS-AS and GLS was inversely correlated in clinical samples of pancreatic cancer, while low expression of GLS-AS was associated with poor clinical outcomes. Collectively, our study implicates a novel lncRNA-mediated Myc/GLS pathway, which may serve as a metabolic target for pancreatic cancer therapy, and advances our understanding of the coupling role of lncRNA in nutrition stress and tumorigenesis.

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Section: Introductionmentioning

confidence: 99%

Nutrient Stress–Dysregulated Antisense lncRNA GLS-AS Impairs GLS-Mediated Metabolism and Represses Pancreatic Cancer Progression

et al. 2019

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“… 28 The dysregulation of transporter and calcium channel probably increase the availability of nutrients. 29 …”

Section: Discussionmentioning

confidence: 99%

Exploration of the molecular mechanism of prostate cancer based on mRNA and miRNA expression profiles

Zhang¹,

Sun²,

Wang³

et al. 2017

OTT

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Prostate cancer, the second most common cancer in men, has been rarely explored by integrating mRNA and miRNA expression profiles. In this study, we combined two mRNA expression datasets and six documented miRNAs to uncover the comprehensive molecular mechanism of prostate cancer. Results showed that a total of 30 genes were significantly differentially expressed in 49 tumor samples by comparing with 22 normal samples. Importantly, all samples from the two datasets can be clearly classified into two groups, tumor group and normal group, based on the selected differentially expressed genes (DEGs). The miRNA–mRNA regulation network indicated that 4 out of 30 DEGs can be regulated by three miRNAs. In addition, prognostic performance validation using in silico databases showed that the DEGs can significantly differentiate between low-risk and high-risk prostate cancer. In summary, multiple biological processes are probably involved in the development and progression of prostate cancer. First, dysregulation of SV2 can regulate transporter and transmembrane transporter activity and then provide the necessary nutrients for tumor cell proliferation. Second, HOXD10 can induce cell proliferation via TCF-4. Finally, dysregulation of CACNA1D can further suppress tumor apoptosis in prostate cancer. The identification of critical genes and valuable biological processes can be useful for the understanding of the molecular mechanism of prostate cancer.

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“…Increased glucose and glutamine consumption may result in their removal from the environment and other metabolic changes may also contribute to differences in the nutrient landscape observed in tumors [ 225 , 285 ].…”

Section: Figurementioning

confidence: 99%

Karyotype Aberrations in Action: The Evolution of Cancer Genomes and the Tumor Microenvironment

Baudoin

Bloomfield

2021

Genes

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Cancer is a disease of cellular evolution. For this cellular evolution to take place, a population of cells must contain functional heterogeneity and an assessment of this heterogeneity in the form of natural selection. Cancer cells from advanced malignancies are genomically and functionally very different compared to the healthy cells from which they evolved. Genomic alterations include aneuploidy (numerical and structural changes in chromosome content) and polyploidy (e.g., whole genome doubling), which can have considerable effects on cell physiology and phenotype. Likewise, conditions in the tumor microenvironment are spatially heterogeneous and vastly different than in healthy tissues, resulting in a number of environmental niches that play important roles in driving the evolution of tumor cells. While a number of studies have documented abnormal conditions of the tumor microenvironment and the cellular consequences of aneuploidy and polyploidy, a thorough overview of the interplay between karyotypically abnormal cells and the tissue and tumor microenvironments is not available. Here, we examine the evidence for how this interaction may unfold during tumor evolution. We describe a bidirectional interplay in which aneuploid and polyploid cells alter and shape the microenvironment in which they and their progeny reside; in turn, this microenvironment modulates the rate of genesis for new karyotype aberrations and selects for cells that are most fit under a given condition. We conclude by discussing the importance of this interaction for tumor evolution and the possibility of leveraging our understanding of this interplay for cancer therapy.

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Nutrient stress revamps cancer cell metabolism

Cited by 6 publications

References 10 publications

Nutrient Stress–Dysregulated Antisense lncRNA GLS-AS Impairs GLS-Mediated Metabolism and Represses Pancreatic Cancer Progression

Nutrient Stress–Dysregulated Antisense lncRNA GLS-AS Impairs GLS-Mediated Metabolism and Represses Pancreatic Cancer Progression

Exploration of the molecular mechanism of prostate cancer based on mRNA and miRNA expression profiles

Karyotype Aberrations in Action: The Evolution of Cancer Genomes and the Tumor Microenvironment

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