共查询到20条相似文献,搜索用时 31 毫秒
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Inman GJ 《Current opinion in genetics & development》2011,21(1):93-99
TGFβ acts as a potent tumor suppressor and tumor promoter in a context dependent manner. Tumor suppressive functions include inhibition of cell proliferation, induction of apoptosis and regulation of autophagy. As tumors develop they switch their response to TGFβ and utilise this factor as a potent promoter of cell motility, invasion, metastasis and tumor stem cell maintenance. These multifactorial tumor influencing actions of TGFβ involve regulation of an increasing number of signal transduction pathways employing a diverse range of signaling molecules. Understanding the molecular mechanisms of how tumor cells respond to TGFβ and switch their response to this cytokine during disease progression is vital for both the development and the informed use of potentially powerful TGFβ targeted therapeutics. 相似文献
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Sustained low-level expression of interferon-γ promotes tumor development: potential insights in tumor prevention and tumor immunotherapy 总被引:2,自引:0,他引:2
He YF Wang XH Zhang GM Chen HT Zhang H Feng ZH 《Cancer immunology, immunotherapy : CII》2005,54(9):891-897
Although the proinflammatory cytokine interferon- (IFN-) has been generally thought to enhance antitumor immune responses and be involved in antitumor mechanisms of many other immunotherapy molecules, it has also been reported that IFN- could promote tumor immune evasion. In this report, by using an ideal mouse model that expresses IFN- locally in muscle, we demonstrate that sustained low-level expression of IFN- promotes the development of several types of tumor including H22 hepatoma, MA782/5S mammary adenocarcinoma and B16 melanoma. However, transitory expression of IFN- does not have such an effect. On the other hand, sustained high-level expression of IFN- mediates significant antitumor effect on H22 hepatoma. Low level of IFN- upregulates expression of PD-L1, PD-L2, CTLA-4 and Foxp3, which may partly account for the tumor immune evasion promoted by IFN-. Furthermore, blockade of PD-L inhibits IFN-s tumor-promoting effect. Our findings provide a mechanistic link between chronic inflammation and cancer and would have potential implications for cancer prevention and also for the design of cytokine–based cancer immunotherapy. 相似文献
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B Zhou X Xiao L Xu L Zhu L Tan H Tang Y Zhang Q Xie S Yao 《Biosensors & bioelectronics》2012,38(1):389-395
An electrochemical indirect competitive immunoassay protocol as a promising cytosensing strategy was developed to detect integrin β1 expression on human breast cancer MCF-7 cells and adriamycin-resistant human breast cancer MCF-7 (MCF-7/ADR) cells and quantify the cell number. Integrin α5β1 was adsorbed on the gold-nanoparticle modified glassy carbon electrode to bind integrin β1 monoclonal antibody (anti-CD29 mAb). A sandwich structure was then formed using nanocomposites which consisted of horseradish peroxidase (HRP) labeled anti-antibody and gold nanoparticles. HRP bound on the electrode surface could cause an amperometric response of the hydroquinone-H(2)O(2) system. The assembly of the sandwich structure was inhibited by tumor cells to give decreased enzyme-catalytic signals due to the capture of anti-CD29 mAb by integrin β1 on cell membranes. Under optimal conditions the relative current change (S) was proportional to the cell concentration from 1.6×10(3) to 2.0×10(6)cellsmL(-1) with a detection limit of 700cellsmL(-1). Integrin β1 expression in MCF-7/ADR cells was found to be significantly higher than that in MCF-7 cells, indicating the increased adhesion ability of MCF-7/ADR cells. 相似文献
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HGF/SF-Met signaling in tumor progression 总被引:11,自引:0,他引:11
Tumor progression is a multi-step process that requires a sequential selection of specific malignant phenotypes. Met activation may induce different phenotypes depending on tumor stage: inducing proliferation and angiogenesis in primary tumors, stimulating motility to form micrometastases, and regaining the proliferation phenotype to form overt metastases. To study how HGF/SF-induced proliferative phenotypes switch to the invasive phenotype is important for understanding the mechanism of tumor progression and will provide an attractive target for cancer intervention and therapy. 相似文献
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Dingcheng Gao Vivek Mittal Yi Ban Ana Rita Lourenco Shira Yomtoubian Sharrell Lee 《生物学前沿》2018,13(4):277-286
Background
Metastasis is the primary cause of mortality in cancer patients. Therefore, elucidating the genetics and epigenetics of metastatic tumor cells and the mechanisms by which tumor cells acquire metastatic properties constitute significant challenges in cancer research.Objective
To summarize the current understandings of the specific genotype and phenotype of the metastatic tumor cells.Method and Result
In-depth genetic analysis of tumor cells, especially with advances in the next-generation sequencing, have revealed insights of the genotypes of metastatic tumor cells. Also, studies have shown that the cancer stem cell (CSC) and epithelial to mesenchymal transition (EMT) phenotypes are associated with the metastatic cascade.Conclusion
In this review, we will discuss recent advances in the field by focusing on the genomic instability and phenotypic dynamics of metastatic tumor cells.10.
Hélène Roumes Elise Dargelos Laetitia Daury Patrick Cottin 《Experimental cell research》2010,316(9):1587-1599
Rhabdomyosarcoma (RMS) are soft-tissue sarcoma commonly encountered in childhood. RMS cells can acquire invasive behavior and form metastases. The metastatic dissemination implicates many proteases among which are μ-calpain and m-calpain.Study of calpain expression and activity underline the deregulation of calpain activity in RMS. Analysis of kinetic characteristics of RMS cells, compared to human myoblasts LHCN-M2 cells, shows an important migration velocity in RMS cells. One of the major results of this study is the positive linear correlation between calpain activity and migration velocity presenting calpains as a marker of tumor aggressiveness. The RMS cytoskeleton is disorganized. Specifying the role of μ- and m-calpain using antisense oligonucleotides led to show that both calpains up-regulate α- and β-actin in ARMS cells. Moreover, the invasive behavior of these cells is higher than that of LHCN-M2 cells. However, it is similar to that of non-treated LHCN-M2 cells, when calpains are inhibited.In summary, calpains may be involved in the anarchic adhesion, migration and invasion of RMS. The direct relationship between calpain activity and migration velocities or invasive behavior indicates that calpains could be considered as markers of tumor aggressiveness and as potential targets for limiting development of RMS tumor as well as their metastatic behavior. 相似文献
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NF-kappaB: tumor promoter or suppressor? 总被引:7,自引:0,他引:7
Perkins ND 《Trends in cell biology》2004,14(2):64-69
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Hypoxia is a common environmental stress. Particularly, the center of rapidly-growing solid tumors is easily exposed to hypoxic conditions. Hypoxia is well known to attenuate the therapeutic response to radio and chemotherapies including tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) protein. HIF-1α is a critical mediator of the hypoxic response. However, little is known about the function of hypoxia-inducible factor-1α (HIF-1α) on hypoxic inhibition of TRAIL-mediated apoptosis. In this study, we investigated whether hypoxic inhibition of TRAIL-mediated apoptosis can be regulated by modulating HIF-1α protein. Hypoxia- and DEF-induced HIF-1α activation inhibited the TRAIL-mediated apoptosis in SK-N-SH, HeLa, A549 and SNU-638 cells. And also, HIF-1α inactivating reagents including DOX increased the sensitivity to TRAIL protein in tumor cells exposed to hypoxia. Furthermore, knock-down of HIF-1α using lentiviral RNA interference sensitized tumor cells to TRAIL-mediated cell death under hypoxic condition. Taken together, these results indicate that HIF-1α inactivation increased TRAIL sensitivity in hypoxia-induced TRAIL-resistant tumor cells and also suggest that HIF-1α inhibitors may have benefits in combination therapy with TRAIL against hypoxic tumor cells. 相似文献
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Linda Owers Narhi Michael F. Rhode Pamela Hunt Tsutomu Arakawa 《Journal of Protein Chemistry》1989,8(5):669-677
The limited proteolysis of human recombinant TNF- by trypsin yields two stable products resulting from cleavage after Arg6 and Arg44. In solution these two products remain associated together in a trimer with a Stokes' radius slightly greater than the radius of intact TNF- and, therefore, could not be separated from each other under nondenaturing conditions. This limited digest retains at least 20% of the activity of the original TNF- sample, and has a tertiary structure that is similar to that of the native protein by circular dichroism. On the other hand, incorrectly folded, inactive TNF- undergoes extensive digestion following similar treatment with trypsin. These results indicate that the active form of TNF- has a tight core structure which is maintained afterN-terminal cleavage and removal. 相似文献
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Why is PTEN an important tumor suppressor? 总被引:12,自引:0,他引:12
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Hunter A Hendrikse A Renan M Abratt R 《Apoptosis : an international journal on programmed cell death》2006,11(10):1727-1735
Cytotoxic anti-cancer agents induce apoptosis in tumor and normal tissues. Therefore, it is important to investigate which
factors determine these apoptotic processes and hence their likely impact on therapeutic gain. Radiation-induced apoptosis
in tumors may be inhibited due to mutations of apoptotic elements or to tumor microenvironmental conditions arising from vascular
insufficiency. Tumors typically contain regions of hypoxia, low glucose and acidosis. Hypoxic cells compromise treatment partly
because of reduced fixation of damage during radiotherapy and partly because they promote a more malignant phenotype. There
is also evidence that hypoxia may inhibit apoptosis. For some cell types, concurrent hypoxia may modulate radiation-induced
apoptosis while, for others, post-irradiation hypoxia may be required. This may reflect the activity of different apoptotic
pathways. Pathways involving mitochondrial components as well as regulation of SAPK and Fas have been implicated. In addition,
several key stages in apoptosis are sensitive to depletion of cellular energy reserves, which results from hypoxia and low
glucose conditions. There is also evidence that low pH in tumors can interfere with radiation-induced apoptosis, partly through
cell cycle arrest and other undefined mechanisms. Conclusions: Hypoxia, low glucose and acidosis influence radiation-induced apoptosis and thus may be detrimental to radiotherapy. 相似文献
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p63: oncogene or tumor suppressor? 总被引:8,自引:0,他引:8
Mills AA 《Current opinion in genetics & development》2006,16(1):38-44
p53, the original member of the family of genes now known to include p63 and p73, was first heralded as an oncogene because of its potent transformation capabilities and its robust expression in human tumors. However, it was later discovered that only mutant p53 was oncogenic, and that wild type p53 functioned as a tumor suppressor. Decades later, p63, the newest member of this gene family, is involved in a similar controversy: is p63 an oncogene or a tumor suppressor? Recent progress on understanding the in vivo role of p63 in cancer has focused primarily on investigating its involvement in the tumor-suppressive mechanism of apoptosis, by analyzing mouse models to assess its tumor-suppressive capabilities, and by assessing its expression in human cancers. 相似文献