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Loss of Mig6 potentiates lung tumorigenesis by mutant EGFRs in vivo

Wednesday, October 10, 2012 — Poster Session II

Noon – 2:00 p.m

Natcher Conference Center, Building 45




  • T.K. Maity
  • A. Venugopalan
  • A. Ginnakov
  • I. Linnoila
  • J. Webster
  • W. Lockwood
  • R. Biswas
  • C. Cultraro
  • R. Nemati
  • H.E. Varmus
  • U. Guha


As a part of mass spectrometry-based phospho-proteomic screening, we identified Mig6 as a target of mutant EGFR and observed that tyrosine phosphorylation of Mig6 is decreased in response to tyrosine kinase inhibitors (erlotinib) treatment in adenocarcinoma cell lines. Since Mig6 negatively regulates EGFR signaling and is a potential tumor suppressor, we hypothesized that loss of Mig6 cooperates with mutant EGFR to accelerate lung tumorigenesis in vivo. We tested this hypothesis by crossing Mig6-/- mice with doxycycline inducible mutant EGFR mice. We observed that Mig6-/- mice harboring lung tumors induced by mutant EGFRs had shorter overall survival compared to Mig6+/+ or Mig6+/- mice. Further biochemical and immunohistochemical analyses indicated that although loss of Mig6 is associated with the decreased expression of EGFR, the proportion of phosphorylated EGFR, and expression of EGFR downstream signaling components AKT and ERK is increased in Mig6-/- mice. We further postulated that treatment with EGFR tyrosine kinase inhibitor might not be as effective in regression of tumor of Mig6-/- mice compared to Mig6+/+ mice. Therefore, we treated these mice cohorts with erlotinib and observed that the regression of lung tumors was delayed in Mig6-/- mice indicating a poor response to erlotinib treatment. This result confirms our hypothesis.

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