Metabolic landscape of the tumor microenvironment at single cell resolution DOI Creative Commons
Zhengtao Xiao, Ziwei Dai, Jason W. Locasale

et al.

Nature Communications, Journal Year: 2019, Volume and Issue: 10(1)

Published: Aug. 21, 2019

The tumor milieu consists of numerous cell types each existing in a different environment. However, characterization metabolic heterogeneity at single-cell resolution is not established. Here, we develop computational pipeline to study programs single cells. In two representative human cancers, melanoma and head neck, apply this algorithm define the intratumor landscape. We report an overall discordance between analyses cells those bulk tumors with higher activity malignant than previously appreciated. Variation mitochondrial found be major contributor heterogeneity. Surprisingly, expression both glycolytic strongly correlates hypoxia all types. Immune stromal could also distinguished by their features. Taken together analysis establishes framework for characterizing metabolism using data defines principles microenvironment.

Language: Английский

Tissue of origin dictates branched-chain amino acid metabolism in mutantKras-driven cancers DOI Open Access
Jared R. Mayers, Margaret E. Torrence, Laura V. Danai

et al.

Science, Journal Year: 2016, Volume and Issue: 353(6304), P. 1161 - 1165

Published: Sept. 8, 2016

Tumor genetics guides patient selection for many new therapies, and cell culture studies have demonstrated that specific mutations can promote metabolic phenotypes. However, whether tissue context defines cancer dependence on pathways is unknown. Kras activation Trp53 deletion in the pancreas or lung result pancreatic ductal adenocarinoma (PDAC) non–small carcinoma (NSCLC), respectively, but despite same initiating events, these tumors use branched-chain amino acids (BCAAs) differently. NSCLC incorporate free BCAAs into protein as a nitrogen source, whereas PDAC decreased BCAA uptake. These differences are reflected expression levels of catabolic enzymes both mice humans. Loss Bcat1 Bcat2, responsible use, impairs tumor formation, not required arguing origin an important determinant how cancers satisfy their requirements.

Language: Английский

Citations

497
Induction of metastasis, cancer stem cell phenotype, and oncogenic metabolism in cancer cells by ionizing radiation DOI Creative Commons
Su Yeon Lee,

Eui Kyong Jeong,

Min Kyung Ju

et al.

Molecular Cancer, Journal Year: 2017, Volume and Issue: 16(1)

Published: Jan. 13, 2017

Radiation therapy is one of the major tools cancer treatment, and widely used for a variety malignant tumours. Radiotherapy causes DNA damage directly by ionization or indirectly via generation reactive oxygen species (ROS), thereby destroying cells. However, ionizing radiation (IR) paradoxically promotes metastasis invasion cells inducing epithelial-mesenchymal transition (EMT). Metastasis obstacle to successful therapy, closely linked rates morbidity mortality many cancers. ROS have been shown play important roles in mediating biological effects IR. implicated IR-induced EMT, activation several EMT transcription factors—including Snail, HIF-1, ZEB1, STAT3—that are activated signalling pathways, including those TGF-β, Wnt, Hedgehog, Notch, G-CSF, EGFR/PI3K/Akt, MAPK. Cancer that undergo acquire stemness metabolic changes, although these points debated. IR known induce stem cell (CSC) properties, dedifferentiation self-renewal, promote oncogenic metabolism activating EMT-inducing pathways. Much accumulated evidence has alterations associated with CSC phenotypes; specifically, seems be required acquisition phenotypes. can also elicit various changes tumour microenvironment (TME) may affect metastasis. CSC, involved radioresistance; targeting them improve efficacy radiotherapy, preventing recurrence This study focuses on molecular mechanisms CSCs, metabolism, TME. We discuss how EMT/CSC/oncogenic resistance radiotherapy; we review efforts develop therapeutic approaches eliminate adverse effects.

Language: Английский

Citations

485
Mechanisms and Implications of Metabolic Heterogeneity in Cancer DOI Creative Commons
Jiyeon Kim, Ralph J. DeBerardinis

Cell Metabolism, Journal Year: 2019, Volume and Issue: 30(3), P. 434 - 446

Published: Sept. 1, 2019

Language: Английский

Citations

477
TCA Cycle and Mitochondrial Membrane Potential Are Necessary for Diverse Biological Functions DOI Creative Commons
Inmaculada Martínez‐Reyes,

Lauren Diebold,

Hyewon Kong

et al.

Molecular Cell, Journal Year: 2015, Volume and Issue: 61(2), P. 199 - 209

Published: Dec. 24, 2015

Language: Английский

Citations

453
Metabolic landscape of the tumor microenvironment at single cell resolution DOI Creative Commons
Zhengtao Xiao, Ziwei Dai, Jason W. Locasale

et al.

Nature Communications, Journal Year: 2019, Volume and Issue: 10(1)

Published: Aug. 21, 2019

The tumor milieu consists of numerous cell types each existing in a different environment. However, characterization metabolic heterogeneity at single-cell resolution is not established. Here, we develop computational pipeline to study programs single cells. In two representative human cancers, melanoma and head neck, apply this algorithm define the intratumor landscape. We report an overall discordance between analyses cells those bulk tumors with higher activity malignant than previously appreciated. Variation mitochondrial found be major contributor heterogeneity. Surprisingly, expression both glycolytic strongly correlates hypoxia all types. Immune stromal could also distinguished by their features. Taken together analysis establishes framework for characterizing metabolism using data defines principles microenvironment.

Language: Английский

Citations

398