Topic
Cancer cell
About: Cancer cell is a research topic. Over the lifetime, 93402 publications have been published within this topic receiving 3512390 citations. The topic is also known as: cancerous cell & tumor cell.
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TL;DR: An analysis of links among GSH, adaptive responses to stress, molecular mechanisms of invasive cancer cell survival and death, and sensitization of metastatic cells to therapy shows that acceleration of GSH efflux facilitates selective GSH depletion in metastasis cells.
Abstract: The glutathione (GSH) content of cancer cells is particularly relevant in regulating mutagenic mechanisms, DNA synthesis, growth, and multidrug and radiation resistance. In malignant tumors, as compared with normal tissues, that resistance associates in most cases with higher GSH levels within these cancer cells. Thus, approaches to cancer treatment based on modulation of GSH should control possible growth-associated changes in GSH content and synthesis in these cells. Despite the potential benefits for cancer therapy of a selective GSH-depleting strategy, such a methodology has remained elusive up to now.Metastatic spread, not primary tumor burden, is the leading cause of cancer death. For patient prognosis to improve, new systemic therapies capable of effectively inhibiting the outgrowth of seeded tumor cells are needed. Interaction of metastatic cells with the vascular endothelium activates local release of proinflammatory cytokines, which act as signals promoting cancer cell adhesion, extravasation, a...
884 citations
TL;DR: The finding that a diet rich in antioxidants or the elimination of ROS by antioxidant compounds prevents the development of certain cancers provided the setting for subsequent investigation of the tumorigenic actions of reactive oxygen species.
Abstract: The generation of reactive oxygen radicals in mammalian cells profoundly affects numerous critical cellular functions, and the absence of efficient cellular detoxification mechanisms which remove these radicals can result in several human diseases. Growing evidence suggests that reactive oxygen species (ROS) within cells act as second messengers in intracellular signaling cascades which induce and maintain the oncogenic phenotype of cancer cells. ROS are tumorigenic by virtue of their ability to increase cell proliferation, survival, cellular migration, and also by inducing DNA damage leading to genetic lesions that initiate tumorigenicity and sustain subsequent tumor progression. However, it is also known that ROS can induce cellular senescence and cell death and can therefore function as anti-tumorigenic agents. Therefore, the mechanisms by which cells respond to reactive oxygen species depends on the molecular background of cell and tissues, the location of ROS production and the concentration of individual ROS species. Carcinoma cells produce ROS at elevated rates in vitro, and in vivo many tumors appear persistent to oxidative stress. Thus, the finding that a diet rich in antioxidants or the elimination of ROS by antioxidant compounds prevents the development of certain cancers provided the setting for subsequent investigation of the tumorigenic actions of reactive oxygen species. This review outlines the current knowledge on the various roles of ROS in tumor development and progression.
881 citations
TL;DR: Homing of melanoma exosomes to sentinel lymph nodes imposes synchronized molecular signals that effect melanoma cell recruitment, extracellular matrix deposition, and vascular proliferation in the lymph nodes.
Abstract: Exosomes are naturally occurring biological nanovesicles utilized by tumors to communicate signals to local and remote cells and tissues. Melanoma exosomes can incite a proangiogenic signaling program capable of remodeling tissue matrices. In this study, we show exosome-mediated conditioning of lymph nodes and define microanatomic responses that license metastasis of melanoma cells. Homing of melanoma exosomes to sentinel lymph nodes imposes synchronized molecular signals that effect melanoma cell recruitment, extracellular matrix deposition, and vascular proliferation in the lymph nodes. Our findings highlight the pathophysiologic role and mechanisms of an exosome-mediated process of microanatomic niche preparation that facilitates lymphatic metastasis by cancer cells.
879 citations
Journal Article•
TL;DR: The c-Myc oncogenic transcription factor, which is known to regulate microRNAs and stimulate cell proliferation, transcriptionally represses miR-23a and miB-23b, resulting in greater expression of their target protein, mitochondrial glutaminase, in human P-493 B lymphoma cells and PC3 prostate cancer cells, which leads to upregulation of glutamine catabolism.
Abstract: Notwithstanding the renewed interest in the Warburg effect, which describes the propensity for cancer cells to avidly metabolize glucose to lactate, cancer cells also depend on continued mitochondrial function for metabolism, specifically glutaminolysis that catabolizes glutamine to generate ATP and lactate. Glutamine is a major source for energy, carbon and nitrogen for anabolic processes in cancer cells, but the regulation of glutamine metabolism is not well understood. Here, we report that the c-Myc oncogenic transcription factor regulates glutamine metabolism by a previously unsuspected mechanism which involves c-Myc suppression of miR-23 microRNAs that target and inhibit mitochondrial glutaminase, or GLS, the first enzyme that catabolizes glutamine. c-Myc also transactivates expression of glutamine transporter genes. We studied the human P-493 B cells that bear a tetracycline-repressible c-Myc construct, such that tetracycline withdrawal induces c-Myc and mitochondrial biogenesis followed by cell proliferation. We found through analyzing the mitochondrial proteome that GLS was increased dramatically in response to c-Myc induction. siRNA targeting GLS1 diminishes cell proliferation and increased apoptosis, indicating that GLS1 is necessary for Myc induced cell proliferation. GLS converts glutamine to glutamate that is further catabolized through the TCA cycle for the production of ATP or serves as substrate for glutathione synthesis. In this regard, depletion of glutamine significantly diminished proliferation of P-493 cell and the human prostate PC3 cancer cell line. Although GLS protein levels are induced >10-fold by c-Myc in P-493 cells, GLS1 mRNA did not vary significantly, suggesting that regulation of GLS protein levels by c-Myc is post-transcriptional. We document that c-Myc transcriptionally represses miR-23, which can inhibit the expression of GLS protein through targeting the 3\#8217;UTR. In addition to the responses of wild-type and miR-23 seed sequence mutant luciferase-GLS1-3\#8217;UTR reporter constructs, antisense miR-23 LNA oligonucleotides were able to elevate GLS protein levels in low c-Myc expressing P493 and PC3 cells, indicating that GLS1 mRNA is a target of miR-23 that inhibits glutaminase translation. Since miR-23 expression is decreased in human prostate cancer, we immunoblotted and found a correlation between c-Myc and GLS protein levels in human prostate cancer samples as compared with lowered expression in the corresponding normal prostate tissues. The unique means by which Myc regulates GLS uncovers a previously unsuspected link between Myc regulation of miRNAs, glutamine metabolism, and energy and reactive oxygen species (ROS) homeostasis and provides a regulatory mechanism involving c-Myc and miRNAs for elevated expression of glutaminase and glutamine metabolism in human cancers. Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr LB-186.
878 citations
TL;DR: It is shown that coexpression of Slug and Sox9 promotes the tumorigenic and metastasis-seeding abilities of human breast cancer cells and is associated with poor patient survival, providing direct evidence that human breast cancers stem cells are controlled by key regulators similar to those operating in normal murine MaSCs.
870 citations