May 23, 2013

Link discovered between MEN1 and much-studied Hedgehog signal pathway

Menin Epigenetically Represses Hedgehog Signaling in MEN1 Tumor Syndrome
-Xianxin Hua, MD, PhD, Buddha Gurung, PhD, Perelman School of Medicine, University of Pennsylvania
Cancer Research April 15, 2013 73:2650-2658; Published OnlineFirst April 15, 2013;

Link discovered between MEN1 and much-studied cell pathway
A research team led by Xianxin Hua, MD, PhD, associate professor of Cancer Biology at the Abramson Family Cancer Research Institute, report in Cancer Research that menin suppresses signaling in the much-studied Hedgehog pathway in endocrine organs.

  • "This study uncovered a new layer of regulation of pro-proliferative genes by menin via the Hedgehog signaling pathway," Hua says.
  • "These pro-replication genes are regulated through GAS1 and PRMT5."
  • The GAS1 protein promotes Hedgehog signaling.
  • Menin interacts with the methylating enzyme PRMT5, and binds to the promoter of the Gas1 gene, inhibiting Gas1 gene transcription.
  • By inhibiting Gas1 expression, menin and PRMT5 inhibit the pathway's tendency towards cell proliferation.
  • Mutant menin proteins are impaired in their ability to interact with PRMT5, and lead to increased Hedgehog signaling and cell proliferation.
  • Hua's team found that treating a mouse model of human MEN1 with a Hedgehog pathway inhibitor called Erivedge reduced proliferation of tumor cells and blood insulin levels. Hua says that this suggests a potential new treatment for MEN1 patients.