Glioblastoma multiforme in the Dock

November 14, 2011

Glioblastoma multiforme (GBM) is the most common malignant brain cancer in humans. Patients with GBM have a poor prognosis because it is a highly aggressive form of cancer that is commonly resistant to current therapies.

A team of researchers -- led by Bo Hu and Shi-Yuan Cheng, at the University of Pittsburgh Cancer Institute, Pittsburgh -- has now identified a molecular pathway that drives the aggressive cancerous nature of a substantial proportion of glioblastomas; specifically, those that overexpress the protein PDGFR-alpha. This pathway could represent a new for treating individuals with glioblastomas that overexpress PDGFR-alpha.

PDGFR-alpha is overexpressed in a substantial proportion of GBMs, and overexpression of this protein is associated with a and shorter survival time. Hu, Cheng, and colleagues found that PDGFR-alpha signaling in human glioblastoma cells triggered a signaling cascade that involved phosphorylation of the protein Dock180 at tyrosine residue 1811 (Dock180Y1811) and downstream activation of the protein Rac1, which led to tumor cell growth and invasion. In human glioblastoma cells, if Dock180 was manipulated so that it could not be phosphorylated at tyrosine residue 1811 PDGFR-alpha failed to promote tumor growth, survival, and invasion. Thus, these data define a signaling pathway of importance in driving the aggressive cancerous nature of glioblastomas that overexpress PDGFR-alpha.

Explore further: Researchers find potential therapeutic target for controlling obesity

More information: Activation of Rac1 by Src-dependent phosphorylation of Dock180Y1811 mediates PDGFR-alpha–stimulated glioma tumorigenesis in mice and humans, Journal of Clinical Investigation.

Related Stories

Recommended for you

Genetic sequencing reveals drug resistance growth

May 25, 2016

The rate at which genetically mutated cancer cells grow may help explain why patients with a common form of leukemia develop treatment resistance, according to new research led by a Weill Cornell Medicine investigator. The ...

Taking control of key protein stifles cancer spread in mice

May 20, 2016

For cancer to spread, the cells that take off into the bloodstream must find a tissue that will permit them to thrive. They don't just go looking, though. Instead, they actively prepare the tissue, in one case by co-opting ...

Cancer can be combated with reprogrammed macrophage cells

May 20, 2016

Researchers at Karolinska Institutet have generated antibodies that reprogramme a type of macrophage cell in the tumour, making the immune system better able to recognise and kill tumour cells. The study, which is published ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.