DF/HCC Program Affiliation

Member, Cancer Genetics Program

Research Abstract

My laboratory is interested in the role of the cytoskeleton:membrane interface in cancer development and progression. To that end we have focused on the Nf2 tumor suppressor and its family members, ezrin, radixin and moesin (the ERM proteins) which localize to the cytoskeleton:membrane interface. The study of Nf2 function in the mouse has revealed tumorigenic and metastatic consequences upon it's loss. The function of the ERM proteins has recently been linked to that of the Ras-related Rho-GTPase which functions in cytoskeletal reorganization and in regulating several well studied molecular signaling pathways. The study of Nf2 function in wild-type cells and the analysis of Nf2-mutant cells derived from these mice has allowed us to link the function of the Nf2 protein (dubbed merlin) to signaling via the Rho family member Rac. This is particularly intriguing given the established relationship between Rac function and cell motility and metastasis. Our efforts are focused on better delineating the molecular function of Nf2 utilizing cell culture and in vitro systems, and utilizing this information to molecularly dissect Nf2-associated tumorigenesis and metastasis in vivo.

Publications

• Curto M, Cole BK, Lallemand D, Liu CH, McClatchey AI. Contact-dependent inhibition of EGFR signaling by Nf2/Merlin. J Cell Biol 2007 Jun 4; 177(5):893-903
  PMID: 17548515
• Bonilha VL, Rayborn ME, Saotome I, McClatchey AI, Hollyfield JG. Microvilli defects in retinas of ezrin knockout mice. Exp Eye Res 2006 Apr; 82(4):720-9
  PMID: 16289046
• McClatchey AI, Saotome I, Mercer K, Crowley D, Gusella JF, Bronson RT, Jacks T. Mice heterozygous for a mutation at the Nf2 tumor suppressor locus develop a range of highly metastatic tumors. Genes Dev 1998 Apr 15; 12(8):1121-33
  PMID: 9553042
• McClatchey AI, Saotome I, Ramesh V, Gusella JF, Jacks T. The Nf2 tumor suppressor gene product is essential for extraembryonic development immediately prior to gastrulation. Genes Dev 1997 May 15; 11(10):1253-65
  PMID: 9171370