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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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Journal ArticleDOI
30 May 2013-Nature
TL;DR: In this paper, it was shown that Ras-transformed cells use macropinocytosis to transport extracellular protein into the cell, yielding amino acids including glutamine that can enter central carbon metabolism.
Abstract: Macropinocytosis is a highly conserved endocytic process by which extracellular fluid and its contents are internalized into cells through large, heterogeneous vesicles known as macropinosomes. Oncogenic Ras proteins have been shown to stimulate macropinocytosis but the functional contribution of this uptake mechanism to the transformed phenotype remains unknown. Here we show that Ras-transformed cells use macropinocytosis to transport extracellular protein into the cell. The internalized protein undergoes proteolytic degradation, yielding amino acids including glutamine that can enter central carbon metabolism. Accordingly, the dependence of Ras-transformed cells on free extracellular glutamine for growth can be suppressed by the macropinocytic uptake of protein. Consistent with macropinocytosis representing an important route of nutrient uptake in tumours, its pharmacological inhibition compromises the growth of Ras-transformed pancreatic tumour xenografts. These results identify macropinocytosis as a mechanism by which cancer cells support their unique metabolic needs and point to the possible exploitation of this process in the design of anticancer therapies.

1,227 citations

Journal Article
TL;DR: The results suggest that tumour cells contain Hsp90 complexes in an activated, high-affinity conformation that facilitates malignant progression, and that may represent a unique target for cancer therapeutics.
Abstract: 5628 Heat shock protein 90 (Hsp90) is a molecular chaperone that plays a key role in the conformational maturation of oncogenic signaling proteins including HER-2, Akt, Raf-1, Bcr-Abl, and mutated p53. The Hsp90 inhibitor 17-allylaminogeldanamycin (17-AAG) binds Hsp90 and induces proteasomal degradation of Hsp90 ‘client’ proteins. Although Hsp90 is highly expressed in most cells, Hsp90 inhibitors selectively kill cancer cells, and 17-AAG is currently in Phase I clinical trials. However, the molecular basis of the tumor selectivity of Hsp90 inhibitors is unknown. The selective retention of 17-AAG in subcutaneous tumor masses in vivo suggests the existence of a drug ‘sink’ in tumor cells. Here we report that Hsp90 derived from tumor cells and clinical cancer biopsies has a 100-fold higher binding affinity for 17-AAG than does Hsp90 from normal cells and tissues. Furthermore, the cytotoxic activity of 17-AAG correlates closely with the binding affinity of the drug to Hsp90 isolated from different cells. This binding affinity change is induced by association of Hsp90 with it’s co-chaperone proteins since tumor Hsp90 is present entirely in multi-chaperone complexes with high ATPase activity, whereas Hsp90 from normal tissues is in a latent, uncomplexed state. In vitro reconstitution of chaperone complexes with Hsp90 resulted in increased binding affinity to 17-AAG, and increased ATPase activity. Additional experiments addressing the relative contribution of cell cycling, oncoprotein overexpression and stress to the activation of Hsp90 will also be presented. We propose a model of Hsp90-dependent malignant progression in which, as tumor cells gradually accumulate mutant and overexpressed signaling proteins, Hsp90 becomes engaged in active chaperoning and stabilization of oncoproteins, and adopts a novel high-affinity form induced by bound co-chaperone proteins. Interestingly, dependence on the activated, high affinity chaperone could make Hsp90 an ’Achilles heel’ of tumor cells, driving the selective accumulation and bioactivity of pharmacological Hsp90 inhibitors, and making tumor Hsp90 a unique cancer target.

1,225 citations

Journal ArticleDOI
TL;DR: At the early stages of carcinogenesis, cell-intrinsic barriers to tumour development seem to be associated with stimulation of an active antitumour immune response, whereas overt tumours development seems to correlate with changes in the immunogenic properties of tumour cells.
Abstract: Numerous innate and adaptive immune effector cells and molecules participate in the recognition and destruction of cancer cells, a process that is known as cancer immunosurveillance. But cancer cells avoid such immunosurveillance through the outgrowth of poorly immunogenic tumour-cell variants (immunoselection) and through subversion of the immune system (immunosubversion). At the early stages of carcinogenesis, cell-intrinsic barriers to tumour development seem to be associated with stimulation of an active antitumour immune response, whereas overt tumour development seems to correlate with changes in the immunogenic properties of tumour cells. The permanent success of treatments for cancer might depend on using immunogenic chemotherapy to re-establish antitumour immune responses.

1,213 citations

Journal ArticleDOI
25 May 2012-Science
TL;DR: Glycine consumption and expression of the mitochondrial glycine biosynthetic pathway was identified as strongly correlated with rates of proliferation across cancer cells, and higher expression of this pathway was associated with greater mortality in breast cancer patients.
Abstract: Metabolic reprogramming has been proposed to be a hallmark of cancer, yet a systematic characterization of the metabolic pathways active in transformed cells is currently lacking. Using mass spectrometry, we measured the consumption and release (CORE) profiles of 219 metabolites from media across the NCI-60 cancer cell lines, and integrated these data with a preexisting atlas of gene expression. This analysis identified glycine consumption and expression of the mitochondrial glycine biosynthetic pathway as strongly correlated with rates of proliferation across cancer cells. Antagonizing glycine uptake and its mitochondrial biosynthesis preferentially impaired rapidly proliferating cells. Moreover, higher expression of this pathway was associated with greater mortality in breast cancer patients. Increased reliance on glycine may represent a metabolic vulnerability for selectively targeting rapid cancer cell proliferation.

1,208 citations

Journal ArticleDOI
TL;DR: All human solid tumor cells require CD47 expression to suppress phagocytic innate immune surveillance and elimination, showing that CD47 is a commonly expressed molecule on all cancers, its function to blockphagocytosis is known, and blockade of its function leads to tumor cell phagcytosis and elimination.
Abstract: CD47, a "don't eat me" signal for phagocytic cells, is expressed on the surface of all human solid tumor cells Analysis of patient tumor and matched adjacent normal (nontumor) tissue revealed that CD47 is overexpressed on cancer cells CD47 mRNA expression levels correlated with a decreased probability of survival for multiple types of cancer CD47 is a ligand for SIRPα, a protein expressed on macrophages and dendritic cells In vitro, blockade of CD47 signaling using targeted monoclonal antibodies enabled macrophage phagocytosis of tumor cells that were otherwise protected Administration of anti-CD47 antibodies inhibited tumor growth in orthotopic immunodeficient mouse xenotransplantation models established with patient tumor cells and increased the survival of the mice over time Anti-CD47 antibody therapy initiated on larger tumors inhibited tumor growth and prevented or treated metastasis, but initiation of the therapy on smaller tumors was potentially curative The safety and efficacy of targeting CD47 was further tested and validated in immune competent hosts using an orthotopic mouse breast cancer model These results suggest all human solid tumor cells require CD47 expression to suppress phagocytic innate immune surveillance and elimination These data, taken together with similar findings with other human neoplasms, show that CD47 is a commonly expressed molecule on all cancers, its function to block phagocytosis is known, and blockade of its function leads to tumor cell phagocytosis and elimination CD47 is therefore a validated target for cancer therapies

1,206 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
20233,549
20225,645
20216,773
20207,065
20196,724
20186,305