Link between inherited endocrine tumour syndrome and much-studied cell pathway (EurekAlert, 24 April 2013)

Menin’s anti-proliferative activity may be mediated through the well-characterised Hedgehog pathway, according to new research from the US. In addition, blocking Hedgehog activity in a mouse model of Multiple Endocrine Neoplasia type 1 (MEN1) provides proof-of-concept results and a potential avenue for therapeutic intervention.

First identifying the suppression of GAS1 by menin in murine pancreatic islets, the researchers from the University of Pennsylvania Perelman School of Medicine, led by Xianxin Hua, MD, PhD, discovered from the literature that GAS1 mediates the pro-proliferative Hedgehog pathway.

This latest study, published in Cancer Research, confirms that ablation of menin in murine pancreatic islets increases Hedgehog signalling, and goes on to characterise the complex by which menin promotes methylation of the Gas1 promoter and consequently suppresses GAS1-mediated expression of Hedgehog. Erivedge (an FDA-approved Hedgehog pathway inhibitor for metastatic or locally advanced basal cell carcinoma) was able to provide proof-of-concept results in a murine model of MEN1 by reducing islet cell tumour mass and fasting insulin levels.

The coupling of a poorly-understood cancer gene with a well-characterised pathway by Hua et al represents a serendipitously economic leap forward in the understanding of MEN1 and sporadic neuroendocrine tumours and their therapeutic leads.

Source: EurekAlert

Paper indexed in PubMed (Hua et al (2013) Cancer Research 73; 2650-8)