CONTEXT: Low tumoral expression of mitogen-inducible gene-6 (Mig-6) is associated with papillary thyroid cancer (PTC) recurrence after thyroidectomy. OBJECTIVE: We hypothesize that Mig-6 behaves as a tumor suppressor in PTC. DESIGN: Mig-6 expression and promoter methylation status were compared in 31 PTC specimens with matched normal thyroid tissue from the same patient. The impact of Mig-6 loss and gain of function on nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) activation, global tyrosine kinase phosphorylation, and cellular invasion was determined in vitro. RESULTS: Mig-6 protein was abundant in all normal thyroid specimens, whereas 77% of PTC had low Mig-6 expression. Mig-6 promoter methylation was found in 79% of PTC with low Mig-6 expression. Low Mig-6 expression in PTC specimens was associated with low NF-κB activity but high levels of epidermal growth factor receptor (EGFR) and ERK phosphorylation. Mig-6 expression inversely correlated with PTC size but had no association with other clinicopathological variables including age, extrathyroidal extension, lymphovascular invasion, or histological subtype. Mig-6 knockdown in thyroid cancer cell lines resulted in EGFR phosphorylation and diminished NF-κB activity, whereas Mig-6 overexpression had the opposite effects. Mig-6 knockdown activated ErbB2, Met, and Src phosphorylation. Furthermore, Mig-6 regulated ERK phosphorylation independent from its effects on EGFR. Mig-6 knockdown promoted cellular proliferation, as determined by clonogenic survival. Lastly, Mig-6 knockdown increased matrix metalloproteinase-2 and -9 activities and increased cellular invasion. CONCLUSIONS: Mig-6 has tumor suppressor-like activity in PTC. In vivo studies are required to confirm that Mig-6 is a putative tumor suppressor in PTC, and future studies should investigate the utility of Mig-6 as a diagnostic marker.
CONTEXT: Low tumoral expression of mitogen-inducible gene-6 (Mig-6) is associated with papillary thyroid cancer (PTC) recurrence after thyroidectomy. OBJECTIVE: We hypothesize that Mig-6 behaves as a tumor suppressor in PTC. DESIGN:Mig-6 expression and promoter methylation status were compared in 31 PTC specimens with matched normal thyroid tissue from the same patient. The impact of Mig-6 loss and gain of function on nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) activation, global tyrosine kinase phosphorylation, and cellular invasion was determined in vitro. RESULTS:Mig-6 protein was abundant in all normal thyroid specimens, whereas 77% of PTC had low Mig-6 expression. Mig-6 promoter methylation was found in 79% of PTC with low Mig-6 expression. Low Mig-6 expression in PTC specimens was associated with low NF-κB activity but high levels of epidermal growth factor receptor (EGFR) and ERK phosphorylation. Mig-6 expression inversely correlated with PTC size but had no association with other clinicopathological variables including age, extrathyroidal extension, lymphovascular invasion, or histological subtype. Mig-6 knockdown in thyroid cancer cell lines resulted in EGFR phosphorylation and diminished NF-κB activity, whereas Mig-6 overexpression had the opposite effects. Mig-6 knockdown activated ErbB2, Met, and Src phosphorylation. Furthermore, Mig-6 regulated ERK phosphorylation independent from its effects on EGFR. Mig-6 knockdown promoted cellular proliferation, as determined by clonogenic survival. Lastly, Mig-6 knockdown increased matrix metalloproteinase-2 and -9 activities and increased cellular invasion. CONCLUSIONS:Mig-6 has tumor suppressor-like activity in PTC. In vivo studies are required to confirm that Mig-6 is a putative tumor suppressor in PTC, and future studies should investigate the utility of Mig-6 as a diagnostic marker.
Authors: Chi-Iou Lin; Justine A Barletta; Matthew A Nehs; Zachary S Morris; David B Donner; Edward E Whang; Jae-wook Jeong; Shioko Kimura; Francis D Moore; Daniel T Ruan Journal: Surgery Date: 2011-12 Impact factor: 3.982
Authors: Malgorzata Milewska; David Romano; Ana Herrero; Maria Luisa Guerriero; Marc Birtwistle; Franz Quehenberger; Stefan Hatzl; Boris N Kholodenko; Oreste Segatto; Walter Kolch; Armin Zebisch Journal: PLoS One Date: 2015-06-12 Impact factor: 3.240
Authors: Mitesh J Borad; Mia D Champion; Jan B Egan; Winnie S Liang; Rafael Fonseca; Alan H Bryce; Ann E McCullough; Michael T Barrett; Katherine Hunt; Maitray D Patel; Scott W Young; Joseph M Collins; Alvin C Silva; Rachel M Condjella; Matthew Block; Robert R McWilliams; Konstantinos N Lazaridis; Eric W Klee; Keith C Bible; Pamela Harris; Gavin R Oliver; Jaysheel D Bhavsar; Asha A Nair; Sumit Middha; Yan Asmann; Jean-Pierre Kocher; Kimberly Schahl; Benjamin R Kipp; Emily G Barr Fritcher; Angela Baker; Jessica Aldrich; Ahmet Kurdoglu; Tyler Izatt; Alexis Christoforides; Irene Cherni; Sara Nasser; Rebecca Reiman; Lori Phillips; Jackie McDonald; Jonathan Adkins; Stephen D Mastrian; Pamela Placek; Aprill T Watanabe; Janine Lobello; Haiyong Han; Daniel Von Hoff; David W Craig; A Keith Stewart; John D Carpten Journal: PLoS Genet Date: 2014-02-13 Impact factor: 5.917