Cancer of the pancreas is a form of cancer that has few treatment options and a poor prognosis. It is linked to two particularly common cellular changes: mutations in a family of cancer genes called RAS and increased activity in the “Hedgehog” signalling pathway, a molecular signal transmission mechanism that is normally only activated during embryonic growth.

The new study, which is published in the journal Nature Structural & Molecular Biology, shows how RAS and the Hedgehog pathway interact in the development of pancreatic cancer in mice. Activation of cancer genes in the RAS family causes the tumour cells to secrete the factor (SHH) that activates Hedgehog signalling, and shuts off the tumour cell’s own ability to respond to this type of stimulation.

The blocking of the Hedgehog response helps, in this phase, to secure the survival of the tumour cells while the surrounding cells are stimulated to grow. In a later phase, when the tumour has become more aggressive, the block is lifted so that tumour cell growth is also precipitated though Hedgehog signalling. The scientists have also identified the proteins that govern the tumour cells’ sensitivity to SHH.

One of the reasons for the poor prognosis associated with pancreatic cancer is that the disease is hard to detect at an early stage. The researchers believe that their results can be of significance to the development of better diagnostic methods and treatment strategies.

Publication: ’DYRK1B-dependent shift of Hedgehog signaling from an autocrine towards a paracrine mode by mutant RAS’, Matthias Lauth, Åsa Bergström, Takashi Shimokawa, Ulrica Tostar, Qianren Jin, Volker Fendrich, Carmen Guerra, Mariano Barbacid and Rune Toftgård, Nature Structural & Molecular Biolog, AOP 30 April 2010, doi. 10.1038/nsmb.1833.

For further information, please contact:

Professor Rune Toftgård
Department of Bioscience and Nutrition (BioNut)
Tel: +46 (0)8-608 91 52, mobile +46 (0)708-720533
Email: Rune.Toftgard@ki.se

Press Officer Katarina Sternudd
Tel: +46 (0)8-524 838 95
Email: katarina.sternudd@ki.se

Karolinska Institutet is one of the world’s leading medical universities. Its mission is to contribute to the improvement of human health through research and education. Karolinska Institutet accounts for over 40 per cent of the medical academic research conducted in Sweden, and offers the country’s broadest range of education in medicine and health sciences. Since 1901 the Nobel Assembly at Karolinska Institutet has selected the Nobel laureates in Physiology or Medicine.

CAPTION: Rune Toftgård, photo by Erik Cronberg.