Understanding How Neuro Cells Turn Cancerous

Scientists from the Sloan-Kettering Institute for Cancer Research in New York with the help of Plymouth University Peninsula Schools of Medicine and Dentistry have completed research which for the first time brings us nearer to understanding how some cells in the brain and nervous system become cancerous.

The results of their study are published in the journal Cancer Cell.

The research team led by Sloan-Kettering researchers studied a tumor suppressor called Merlin.

The results of the study have identified a new mechanism whereby Merlin suppresses tumors, and that the mechanism operates within the nucleus. The research team has discovered that unsuppressed tumor cells increase via a core signaling system, the hippo pathway, and they have identified the route and method by which this signaling occurs.

By identifying the signaling system and understanding how, when present, Merlin suppresses it, the way is open for research into drug therapies which may suppress the signalling in a similar way to Merlin.

tumor suppressors exist in cells to prevent abnormal cell division in our bodies. The loss Merlin leads to tumors in many cell types within our nervous systems. There are two copies of a tumor suppressor, one on each chromosome that we inherit from our parents. The loss of Merlin can be caused by random loss of both copies in a single cell, causing sporadic tumors, or by inheriting one abnormal copy and losing the second copy throughout our lifetime as is seen in the inherited condition of neurofibromatosis type 2 (NF2).

No effective therapy for these tumors exists, other than repeated invasive surgery aiming at a single tumor at a time and which is unlikely to eradicate the full extent of the tumors, or radiotherapy.

Professor Oliver Hanemann, Director of the Institute of Translational and Stratified Medicine at Plymouth University Peninsula Schools of Medicine and Dentistry, and who led the Plymouth aspect of the study, commented: "We have known for some time that the loss of the tumor suppressor Merlin resulted in the development of nervous system tumors, and we have come tantalisingly close to understanding how this occurs. Our joint study with colleagues at the Sloan-Kettering Institute for Cancer Research shows for the first time how this mechanism works. By understanding the mechanism, we can use this knowledge to develop effective drug therapies -- in some cases adapting existing drugs -- to treat patients for whom current therapies are limited and potentially devastating."

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University of Plymouth   Original reporting by: Andrew Gould

Publication

Wei Li, Jonathan Cooper, Lu Zhou, Chenyi Yang, Hediye Erdjument-Bromage, David Zagzag, Matija Snuderl, Marc Ladanyi, C. Oliver Hanemann, Pengbo Zhou, Matthias A. Karajannis, Filippo G. Giancotti. Merlin/NF2 Loss-Driven Tumorigenesis Linked to CRL4DCAF1-Mediated Inhibition of the Hippo Pathway Kinases Lats1 and 2 in the Nucleus.   Cancer Cell, Published July 14 2014. doi: 10.1016/j.ccr.2014.05.001