New research finds way to switch off breast cancer and leukaemia

Aug 11 2008

Australian scientists have identified a way of switching off a molecule, which plays a key role in the process that triggers breast cancer and certain forms of leukaemia.

The researchers from the Garvan Institute of Medical Research in Sydney have found a new way of blocking signals to the molecule, stopping it from succeeding in its role of cell proliferation.

The molecule, known as Gab2, plays a part in the development of breast cancer along with the major breast cancer oncogene, HER2, the target of the drug Herceptin.

The researchers led by Professor Roger Daly, have been examining exactly how Gab2 functions, and how to stop it operating.

Professor Daly says Gab2 is a signalling protein, which is involved in transmitting signals from the cell surface to the interior of the cell, instructing it to do specific things, such as divide or migrate.

Professor Daly says Gab2 has a number of signalling roles in normal cells throughout the body, and is usually switched off when it's not needed and the team set out to discover how the body switches off Gab2 in order to mimic that process in abnormal cells.

Daly says they have identified a completely new mechanism for switching off Gab2 which uses another molecule that attaches to Gab2 and acts as a shield, preventing it from transmitting further proliferative signals.

The Professor says this 'off switch', is called 14-3-3, and is used to disable Gab2 in a number of cellular settings, when it is no longer needed.

He says as Gab2 plays key roles in signalling systems that underpin both normal physiological responses and oncogenesis, it's very important to understand its control mechanisms and the next step will be to obtain more structural information about how 14-3-3 shields Gab2.

Professor Daly says once that is known, it should be possible to design drugs to combat Gab2-activated diseases in new ways.

The finding is published online in the EMBO Journal.