The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Manfred Kunz - One of the best experts on this subject based on the ideXlab platform.
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microrna let 7b targets important cell cycle molecules in malignant melanoma cells and interferes with Anchorage Independent Growth
Cell Research, 2008Co-Authors: Julia Schultz, Peter Lorenz, Gerd Gross, Saleh M Ibrahim, Manfred KunzAbstract:MicroRNA let-7b targets important cell cycle molecules in malignant melanoma cells and interferes with Anchorage-Independent Growth
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MicroRNA let-7b targets important cell cycle molecules in malignant melanoma cells and interferes with Anchorage-Independent Growth
Cell Research, 2008Co-Authors: Julia Schultz, Peter Lorenz, Gerd Gross, Saleh Ibrahim, Manfred KunzAbstract:A microRNA expression screen was performed analyzing 157 different microRNAs in laser-microdissected tissues from benign melanocytic nevi ( n = 10) and primary malignant melanomas ( n = 10), using quantitative real-time PCR. Differential expression was found for 72 microRNAs. Members of the let-7 family of microRNAs were significantly downregulated in primary melanomas as compared with benign nevi, suggestive for a possible role of these molecules as tumor suppressors in malignant melanoma. Interestingly, similar findings had been described for lung and colon cancer. Overexpression of let-7b in melanoma cells in vitro downregulated the expression of cyclins D1, D3, and A, and cyclin-dependent kinase (Cdk) 4, all of which had been described to play a role in melanoma development. The effect of let-7b on protein expression was due to targeting of 3′-untranslated regions (3′UTRs) of individual mRNAs, as exemplified by reporter gene analyses for cyclin D1. In line with its downmodulating effects on cell cycle regulators, let-7b inhibited cell cycle progression and Anchorage-Independent Growth of melanoma cells. Taken together, these findings not only point to new regulatory mechanisms of early melanoma development, but also may open avenues for future targeted therapies of this tumor.
Chuanshu Huang - One of the best experts on this subject based on the ideXlab platform.
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the ring domain in the anti apoptotic protein xiap stabilizes c myc protein and preserves Anchorage Independent Growth of bladder cancer cells
Journal of Biological Chemistry, 2019Co-Authors: Chao Huang, Guosong Jiang, Xin Liao, Fuqing Zeng, Chuanshu HuangAbstract:X-linked inhibitor of apoptosis protein (XIAP) suppresses apoptosis and plays key roles in the development, Growth, migration, and invasion of cancer cells. Therefore, XIAP has recently attracted much attention as a potential antineoplastic therapeutic target, requiring elucidation of the molecular mechanisms underlying its biological activities. Here, using shRNA-mediated gene silencing, immunoblotting, quantitative RT-PCR, Anchorage-Independent Growth assay, and invasive assay, we found that XIAP's RING domain, but not its BIR domain, is crucial for XIAP-mediated up-regulation of c-Myc protein expression in human bladder cancer (BC) cells. Mechanistically, we observed that the RING domain stabilizes c-Myc by inhibiting its phosphorylation at Thr-58 and that this inhibition is due to activated ERK1/2-mediated phosphorylation of glycogen synthase kinase-3β (GSK-3β) at Ser-9. Functional studies further revealed that c-Myc protein promotes Anchorage-Independent Growth and invasion stimulated by the XIAP RING domain in human BC cells. Collectively, the findings in our study uncover that the RING domain of XIAP supports c-Myc protein stability, providing insight into the molecular mechanism and role of c-Myc overexpression in cancer progression. Our observations support the notion of targeting XIAP's RING domain and c-Myc in cancer therapy.
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X-linked inhibitor of apoptosis protein (XIAP) lacking RING domain localizes to the nuclear and promotes cancer cell Anchorage-Independent Growth by targeting the E2F1/Cyclin E axis
Oncotarget, 2014Co-Authors: Zipeng Cao, Wenjing Luo, Chuanshu Huang, Jingyuan ChenAbstract:// Zipeng Cao 1,2 , Xueyong Li 3 , Jingxia Li 2 , Wenjing Luo 1 , Chuanshu Huang 2 and Jingyuan Chen 1 1 Department of Occupational and Environmental Health and Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi’an, China 2 Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, NY, USA 3 Department of Plastic and Burn Surgery, Tangdu Hospital, Fourth Military Medical University, Xi’an, China Correspondence: Jingyuan Chen, email: // Chuanshu Huang, email: // Keywords : XIAP; RING domain; cell cycle progression; E2F1 Received : March 17, 2014 Accepted : July 16, 2014 Published : July 17, 2014 Abstract The inhibitor of apoptosis protein XIAP (X-linked inhibitor of apoptosis protein) is a well-documented protein that is located in cytoplasm acting as a potent regulator of cell apoptosis. Here, we showed that expressing XIAP with RING (Really Interesting New Gene) domain deletion (XIAP△ RING ) in cancer cells promoted cancer cell Anchorage-Independent Growth and G 1 /S phase transition companied with increasing cyclin e transcription activity and protein expression. Further studies revealed that XIAP△ RING was mainly localized in nuclear with increased binding with E2F1, whereas XIAP with BIR (Baculoviral IAP Repeat) domains deletion (XIAP△ BIRs ) was entirely presented in cytoplasma with losing its binding with E2F1, suggesting that RING domain was able to inhibit BIR domains nuclear localization, by which impaired BIRs binding with E2F1 in cellular nucleus in intact cells. These studies identified a new function of XIAP protein in cellular nucleus is to regulate E2F1 transcriptional activity by binding with E2F1 in cancer cells. Our current finding of an effect of XIAP△ RING expression on cancer cell Anchorage-Independent Growth suggests that overexpression of this protein may contribute to genetic instability associated with cell cycle and checkpoint perturbations, in addition to its impact on cellular apoptosis.
R. Ariel Igal - One of the best experts on this subject based on the ideXlab platform.
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Stearoyl-COA desaturase is involved in the control of proliferation, Anchorage-Independent Growth and survival in human transformed cells
The Journal of biological chemistry, 2005Co-Authors: Natalia Scaglia, R. Ariel IgalAbstract:Saturated and monounsaturated fatty acids are the most abundant fatty acid species in mammalian organisms, and their distribution is regulated by stearoyl-CoA desaturase, the enzyme that converts saturated into monounsaturated fatty acids. A positive correlation between high monounsaturated fatty acid levels and neoplastic transformation has been reported, but little is still known about the regulation of stearoyl-CoA desaturase in cell proliferation and apoptosis, as well as in cancer development. Here we report that simian virus 40-transformed human lung fibroblasts bearing a knockdown of human stearoyl-CoA desaturase by stable antisense cDNA transfection (hSCDas cells) showed a considerable reduction in monounsaturated fatty acids, cholesterol, and phospholipid synthesis, compared with empty vector transfected-simian virus 40 cell line (control cells). hSCDas cells also exhibited high cellular levels of saturated free fatty acids and triacylglycerol. Interestingly, stearoyl-CoA desaturase-depleted cells exhibited a dramatic decrease in proliferation rate and abolition of Anchorage-Independent Growth. Prolonged exposure to exogenous oleic acid did not reverse either the slower proliferation or loss of Anchorage-Independent Growth of hSCDas cells, suggesting that endogenous synthesis of monounsaturated fatty acids is essential for rapid cell replication and invasiveness, two hallmarks of neoplastic transformation. Moreover, apoptosis was increased in hSCDas cells in a ceramide-Independent manner. Finally, stearoyl-CoA desaturase-deficient cells were more sensitive to palmitic acid-induced apoptosis compared with control cells. Our data suggest that, by globally regulating lipid metabolism, stearoyl-CoA desaturase activity modulates cell proliferation and survival and emphasize the important role of endogenously synthesized monounsaturated fatty acids in sustaining the neoplastic phenotype of transformed cells.
Stuart K Calderwood - One of the best experts on this subject based on the ideXlab platform.
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induction of heat shock proteins by heregulin β1 leads to protection from apoptosis and Anchorage Independent Growth
Oncogene, 2005Co-Authors: Abdul Khaleque, Ajit Bharti, Douglas B Sawyer, Jianlin Gong, Ivor J Benjamin, Mary Ann Stevenson, Stuart K CalderwoodAbstract:Elevation of heat shock protein (HSP) levels is widespread in cancer and predicts a poor prognosis and resistance to therapy. We show that HSP elevation in tumor cells can be induced by the highly malignant factor heregulin β1 (HRGβ1), which induces HSP expression through heat shock transcription factor 1 (HSF1). Inactivation of the hsf1 gene prevents HSP induction by HRGβ1. HSP expression is induced through a cascade response initiated by HRGβ1 binding to c-erbB receptors on the cell surface and which leads to the inhibition of intracellular HSF1 antagonist glycogen synthase kinase 3. HSF1 activated by this pathway plays a key role in the protection of cells from apoptosis and the mediation of Anchorage Independent Growth by HRGβ1, indicating a role for HSF1 in this tumorigenic pathway.
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induction of heat shock proteins by heregulin β1 leads to protection from apoptosis and Anchorage Independent Growth
Oncogene, 2005Co-Authors: Abdul Khaleque, Ajit Bharti, Douglas B Sawyer, Jianlin Gong, Ivor J Benjamin, Mary Ann Stevenson, Stuart K CalderwoodAbstract:Elevation of heat shock protein (HSP) levels is widespread in cancer and predicts a poor prognosis and resistance to therapy. We show that HSP elevation in tumor cells can be induced by the highly malignant factor heregulin beta1 (HRGbeta1), which induces HSP expression through heat shock transcription factor 1 (HSF1). Inactivation of the hsf1 gene prevents HSP induction by HRGbeta1. HSP expression is induced through a cascade response initiated by HRGbeta1 binding to c-erbB receptors on the cell surface and which leads to the inhibition of intracellular HSF1 antagonist glycogen synthase kinase 3. HSF1 activated by this pathway plays a key role in the protection of cells from apoptosis and the mediation of Anchorage Independent Growth by HRGbeta1, indicating a role for HSF1 in this tumorigenic pathway.
Julia Schultz - One of the best experts on this subject based on the ideXlab platform.
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microrna let 7b targets important cell cycle molecules in malignant melanoma cells and interferes with Anchorage Independent Growth
Cell Research, 2008Co-Authors: Julia Schultz, Peter Lorenz, Gerd Gross, Saleh M Ibrahim, Manfred KunzAbstract:MicroRNA let-7b targets important cell cycle molecules in malignant melanoma cells and interferes with Anchorage-Independent Growth
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MicroRNA let-7b targets important cell cycle molecules in malignant melanoma cells and interferes with Anchorage-Independent Growth
Cell Research, 2008Co-Authors: Julia Schultz, Peter Lorenz, Gerd Gross, Saleh Ibrahim, Manfred KunzAbstract:A microRNA expression screen was performed analyzing 157 different microRNAs in laser-microdissected tissues from benign melanocytic nevi ( n = 10) and primary malignant melanomas ( n = 10), using quantitative real-time PCR. Differential expression was found for 72 microRNAs. Members of the let-7 family of microRNAs were significantly downregulated in primary melanomas as compared with benign nevi, suggestive for a possible role of these molecules as tumor suppressors in malignant melanoma. Interestingly, similar findings had been described for lung and colon cancer. Overexpression of let-7b in melanoma cells in vitro downregulated the expression of cyclins D1, D3, and A, and cyclin-dependent kinase (Cdk) 4, all of which had been described to play a role in melanoma development. The effect of let-7b on protein expression was due to targeting of 3′-untranslated regions (3′UTRs) of individual mRNAs, as exemplified by reporter gene analyses for cyclin D1. In line with its downmodulating effects on cell cycle regulators, let-7b inhibited cell cycle progression and Anchorage-Independent Growth of melanoma cells. Taken together, these findings not only point to new regulatory mechanisms of early melanoma development, but also may open avenues for future targeted therapies of this tumor.