Metabolic reprogramming of the tumour microenvironment

Xing, Yazhi; Zhao, Shimin; Zhou, Binhua P.; Mi, Jun

doi:10.1111/febs.13402

Cited by 88 publications

(69 citation statements)

References 21 publications

(21 reference statements)

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“…In contrast to tumor cells, the increase in glycolysis within CAFs is not associated with elevated proliferation of CAFs themselves, but strongly promotes tumor growth and metastasis (64). Lactate secretion from CAFs induces a local acidic microenvironment, which can enhance extracellular proteolysis and promotes the acquisition of drug resistance by tumor cells (65).…”

Section: The Reverse Warburg Effectmentioning

confidence: 99%

Metabolic Plasticity as a Determinant of Tumor Growth and Metastasis

et al. 2016

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Cancer cells must adapt their metabolism to meet the energetic and biosynthetic demands that accompany rapid growth of the primary tumor and colonization of distinct metastatic sites. Different stages of the metastatic cascade can also present distinct metabolic challenges to disseminating cancer cells. However, little is known regarding how changes in cellular metabolism, both within the cancer cell and the metastatic microenvironment, alter the ability of tumor cells to colonize and grow in distinct secondary sites. This review examines the concept of metabolic heterogeneity within the primary tumor, and how cancer cells are metabolically coupled with other cancer cells that comprise the tumor and cells within the tumor stroma. We examine how metabolic strategies, which are engaged by cancer cells in the primary site, change during the metastatic process. Finally, we discuss the metabolic adaptations that occur as cancer cells colonize foreign metastatic microenvironments and how cancer cells influence the metabolism of stromal cells at sites of metastasis. Through a discussion of these topics, it is clear that plasticity in tumor metabolic programs, which allows cancer cells to adapt and grow in hostile microenvironments, is emerging as an important variable that may change clinical approaches to managing metastatic disease. Cancer Res; 76(18); 5201-8. Ó2016 AACR.

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Section: The Reverse Warburg Effectmentioning

confidence: 99%

Metabolic Plasticity as a Determinant of Tumor Growth and Metastasis

et al. 2016

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“…Cancer-associated fibroblasts (CAFs), are major components of cancer stromal cells that account for about 40%–50% of the total cell population in cancers (Xing et al, 2015). CAFs are primarily derived from activated quiescent fibroblasts surrounding the cancer cells, and have been shown to directly promote tumor initiation (Bhowmick et al, 2004; Olumi et al, 1999), progression (Dimanche-Boitrel et al, 1994; Orimo et al, 2005), and metastasis (Grum-Schwensen et al, 2005; Olaso et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

Cancer-associated Fibroblasts Promote Irradiated Cancer Cell Recovery Through Autophagy

et al. 2017

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Tumor relapse after radiotherapy is a significant challenge to oncologists, even after recent the advances in technologies. Here, we showed that cancer-associated fibroblasts (CAFs), a major component of cancer stromal cells, promoted irradiated cancer cell recovery and tumor relapse after radiotherapy. We provided evidence that CAFs-produced IGF1/2, CXCL12 and β-hydroxybutyrate were capable of inducing autophagy in cancer cells post-radiation and promoting cancer cell recovery from radiation-induced damage in vitro and in vivo in mice. These CAF-derived molecules increased the level of reactive oxygen species (ROS) post-radiation, which enhanced PP2A activity, repressing mTOR activation and increasing autophagy in cancer cells. Consistently, the IGF2 neutralizing antibody and the autophagy inhibitor 3-MA reduce the CAF-promoted tumor relapse in mice after radiotherapy. Taken together, our findings demonstrated that CAFs promoted irradiated cancer cell recovery and tumor regrowth post-radiation, suggesting that targeting the autophagy pathway in tumor cells may be a promising therapeutic strategy for radiotherapy sensitization.

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“…In this process, fibroblasts become increasingly proliferative, secrete increased ECM proteins and various growth factors and alter their actin cytoskeleton to a more contractile configuration with increased stress fibers, often expressing α-smooth muscle actin (SMA) and fibroblast activation protein (FAP) [8,10]. The biology of activated fibroblasts is intimately linked with the tumor cells via their exchange of growth factors and cyto- kines, as well as other materials such as micro-RNAs (miRNAs) and metabolites (see Figure 2) [5,[11][12][13]. Immune cells (e.g., infiltrating macrophages, lymphocytes, natural killer cells) are recruited to the tumor site by cytokines secreted from cancer cells, fibroblasts and resident macrophages [3,10,14].…”

mentioning

confidence: 99%

Epigenetic Control of the Tumor Microenvironment

2016

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Stromal cells of the tumor microenvironment have been shown to play important roles in both supporting and limiting cancer growth. The altered phenotype of tumorassociated stromal cells (fibroblasts, immune cells, endothelial cells etc.) is proposed to be mainly due to epigenetic dysregulation of gene expression; however, only limited studies have probed the roles of epigenetic mechanisms in the regulation of stromal cell function. We review recent studies demonstrating how specific epigenetic mechanisms (DNA methylation and histone post-translational modification-based gene expression regulation, and miRNA-mediated translational regulation) drive aspects of stromal cell phenotype, and discuss the implications of these findings for treatment of malignancies. We also summarize the effects of epigenetic mechanismtargeted drugs on stromal cells and discuss the consideration of the microenvironment response in attempts to use these drugs for cancer treatment.

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Metabolic reprogramming of the tumour microenvironment

Cited by 88 publications

References 21 publications

Metabolic Plasticity as a Determinant of Tumor Growth and Metastasis

Metabolic Plasticity as a Determinant of Tumor Growth and Metastasis

Cancer-associated Fibroblasts Promote Irradiated Cancer Cell Recovery Through Autophagy

Epigenetic Control of the Tumor Microenvironment

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