The translational landscape of mTOR signalling steers cancer initiation and metastasis

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.     

Identification of two related pentapeptides from the brain with potent opiate agonist activity.

Enkephalin, a natural ligand for opiate receptors is composed of the pentapepides H-Tyr-Gly-Gly-Phe-Met-OH and H-Tyr-Gly-Gly-Phe-Leu-OH. The evidence is based on the determination of the amino acid sequence of natural enkephalin by the dansyl-Edman procedure and by mass spectrometry followed by synthesis and comparison of the natural and synthetic peptides.     

Stimulation of SV40 virus replication in Chinese hamster kidney cells by treatment of the cells with mitomycin C]

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.     

Ethanol-induced changes in plasma glucose,insulin and glucagon in fed and fasted rats

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.