Researchers from the NYU Cancer Institute, an NCI-designated cancer center at NYU Langone Medical Center, have identified a cell cycle-regulated mechanism behind the transformation of normal cells into cancerous cells. The study shows the significant role that protein networks can play in a cell leading to the development of cancer. The study results, published in the October 21 issue of the journal Molecular Cell, suggest that inhibition of the CK1 enzyme may be a new therapeutic target for the treatment of cancer cells formed as a result of a malfunction in the cell’s mTOR signaling pathway.
In the study, NYU Cancer Institute researchers examined certain multi-protein complexes and protein regulators in cancer cells. Researchers identified a major role for the multi-protein complex called SCFβTrCP . It assists in the removal from cancer cells the recently discovered protein DEPTOR, an inhibitor of the mTOR pathway. SCF (Skp1, Cullin1, F-box protein) ubiquitin ligase complexes are responsible for the removal of unnecessary proteins from a cell. This degradation of proteins by the cell’s ubiquitin system controls cell growth and prevents malignant cell transformation. Researchers show that inhibiting the ability of SCFβTrCP to degrade DEPTOR in cells can result in blocking the proliferation of cancer cells. In addition, researchers discovered that the activity of CK1 (Casein Kinase 1), a protein that regulates signaling pathways in most cells, is needed for SCFβTrCP to successfully promote the degradation of DEPTOR.
“Low levels of DEPTOR and high levels of mTOR activity are found in many cancers, including cancers of the breast, prostate, and lung,” said senior study author Michele Pagano, MD, the May Ellen and Gerald Jay Ritter Professor of Oncology and Professor of Pathology at NYU Langone Medical Center and a Howard Hughes Medical Institute Investigator. “It is critical for researchers to better understand how the protein DEPTOR is regulated. Our study shows it would be advantageous to increase the levels of DEPTOR in many types of cancer cells to inhibit mTOR and prevent cell proliferation.”
New research reveals how we make decisions. Birds choosing between berry bushes and investors trading stocks are faced with the same fundamental challenge - making optimal choices in an environment featuring varying costs and benefits. A neuroeconomics study from the Montreal Neurological Institute and Hospital – The Neuro, McGill University, shows that the brain employs two separate regions and two distinct processes in valuing ‘stimuli’ i.e. ‘goods’ (for example, berry bushes), as opposed to valuing the ‘actions,’ needed to obtain the desired option (for example flight paths to the berry bushes). The findings, published in the most recent issue of the Journal of Neuroscience and funded by the Canadian Institutes of Health Research, are vital not only for improving knowledge of brain function, but also for treating and understanding the effects of frontal lobe damage, which can be a feature of common neurological conditions ranging from stroke to traumatic brain injury to dementia.
Decision making - selecting the most valuable option, typically by taking an action - requires value comparisons, but there has been debate about how these comparisons occur in the brain: is value linked to the object itself , or to the action required to get that object. Are choices made between the things we want, or between the actions we take? The dominant model of decision making proposes that value comparisons occur in series, with stimulus value information feeding into actions (the body’s motor system). “So, in this study we wanted to understand how the brain uses value information to make decisions between different actions, and between different objects,” said the study’s lead investigator Dr. Lesley Fellows, neurologist and researcher at The Neuro. “The surprising and novel finding is that in fact these two mechanisms of choice are independent of one another. There are distinct processes in the brain by which value information guides decisions, depending on whether the choice is between objects or between actions.” Dr. Fellows often sees patients with damage to the frontal lobe, where decision making areas of the brain are located. “This finding gives me more insight into what is happening in the brain of my patients, and may lead to new treatments and new ways to care for them and manage their symptoms.”
“Despite the ubiquity and importance of decision making, we have had, until now, a limited understanding of its basis in the brain,” said Fellows. “Psychologists, economists, and ecologists have studied decision making for decades, but it has only recently become a focus for neuroscientists.