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Hsieh AC Liu Y Edlind MP Ingolia NT Janes MR Sher A Shi EY Stumpf CR Christensen C Bonham MJ Wang S Ren P Martin M Jessen K Feldman ME Weissman JS Shokat KM Rommel C Ruggero D 《Nature》2012,485(7396):55-61
The mammalian target of rapamycin (mTOR) kinase is a master regulator of protein synthesis that couples nutrient sensing to cell growth and cancer. However, the downstream translationally regulated nodes of gene expression that may direct cancer development are poorly characterized. Using ribosome profiling, we uncover specialized translation of the prostate cancer genome by oncogenic mTOR signalling, revealing a remarkably specific repertoire of genes involved in cell proliferation, metabolism and invasion. We extend these findings by functionally characterizing a class of translationally controlled pro-invasion messenger RNAs that we show direct prostate cancer invasion and metastasis downstream of oncogenic mTOR signalling. Furthermore, we develop a clinically relevant ATP site inhibitor of mTOR, INK128, which reprograms this gene expression signature with therapeutic benefit for prostate cancer metastasis, for which there is presently no cure. Together, these findings extend our understanding of how the 'cancerous' translation machinery steers specific cancer cell behaviours, including metastasis, and may be therapeutically targeted. 相似文献
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Oncogenic protein tyrosine kinases 总被引:6,自引:0,他引:6
Pulford K Lamant L Espinos E Jiang Q Xue L Turturro F Delsol G Morris SW 《Cellular and molecular life sciences : CMLS》2004,61(23):2939-2953
Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase, the normal role of which remains to be completely elucidated. Although work carried out in mammals suggests a function in neural development, results from studies in Drosophila indicate an additional role in visceral muscle differentiation. The aberrant expression of full-length ALK receptor proteins has been reported in neuroblastomas and glioblastomas, while the occurrence of ALK fusion proteins in anaplastic large cell lymphoma (ALCL) has resulted in the identification of the new tumor entity, ALK-positive ALCL. ALK represents one of few examples of a receptor tyrosine kinase implicated in oncogenesis in both haematopoietic and non-haematopoietic tumors, given that ALK fusions also occur in the mesenchymal tumor known as inflammatory myofibroblastic tumor (IMT). The study of ALK fusion proteins, besides demonstrating their importance in tumor development, has also raised the possibility of new therapeutic treatments for patients with ALK-positive malignancies. 相似文献
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C Lavialle A G Morris H G Suárez R Cassingena 《Comptes rendus des séances de l'Académie des sciences. Série D, Sciences naturelles》1975,281(16):1203-1206
The production of virions by Chinese hamster kidney cells infected with SV 40 DNA is increased 10 to 100 fold by mitomycin C treatment. This observation has been confirmed for different cell clones. The optimum concentration of mitomycin C has been determined. 相似文献
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Summary Orally administered ethanol produced dose-related suppression of IRI levels and elevation of IRG levels in fed and fasting rats. Plasma glucose levels were unaffected in the fasting rats, but a moderate hyperglycemic response accompanied the decline in IRI and the rise in IRG observed in the fed rats.This research was supported in part by a grant from the National Institute on Alcohol Abuse and Alcoholism (AA-3218) and by a supplemental grant from the National Council on Alcoholism. 相似文献
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