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MIG-7 and phosphorylated prohibitin coordinately regulate lung cancer invasion/metastasis

Growth factors and COX-2/PGE2 enhance lung cancer invasion/metastasis via PI3K/Akt and RAS/Raf. Here, we explored their mechanism of action further. We found first that higher levels of migration inducting gene-7 protein (MIG-7) and PHB phosphorylated at threonine 258 (phospho-PHB(T258)) are positiv...

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Autores principales: Ho, Ming-Yi, Liang, Chi-Ming, Liang, Shu-Mei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4381602/
https://www.ncbi.nlm.nih.gov/pubmed/25575814
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author Ho, Ming-Yi
Liang, Chi-Ming
Liang, Shu-Mei
author_facet Ho, Ming-Yi
Liang, Chi-Ming
Liang, Shu-Mei
author_sort Ho, Ming-Yi
collection PubMed
description Growth factors and COX-2/PGE2 enhance lung cancer invasion/metastasis via PI3K/Akt and RAS/Raf. Here, we explored their mechanism of action further. We found first that higher levels of migration inducting gene-7 protein (MIG-7) and PHB phosphorylated at threonine 258 (phospho-PHB(T258)) are positively correlated with advanced stages of human lung cancer in tissue microarray. PGE2 or growth factors such as EGF, HGF and IGF-1 increased complex formation of phospho-PHB(T258) with Ras, phospho-Akt(S473), phospho-Raf-1(S338), MEKK1 and IKKα/β(S176/180) in the raft domain transiently within 1 hour and MIG-7 in the cytosol 12-24 hours later. Association of phospho-PHB(T258) with MEKK1 but not MEKK3 activates IKK/IκB/NF-κB and MEK/ERK to increase cellular COX-2/PGE2 and an E-cadherin suppressor Snail leading to enhancement of epithelial-mesenchymal transition (EMT) and lung cancer migration/invasion. MIG-7, on the other hand, was induced by growth factors and PGE2 via Akt/GSK-3β in a phospho-PHB(T258) independent manner. MIG-7 increased two E-cadherin suppressors ZEB-1 and Twist to enhance EMT and cancer migration/invasion. Downregulating phospho-PHB(T258) and MIG-7 had an additive effect on attenuating lung cancer invasion/metastasis and prolonging the survival of xenograft mice. Phospho-PHB(T258) and MIG-7 may thus play complementary roles in the initiation and sustainment of the effects of growth factors and COX-2/PGE2 on cancer invasion/metastasis.
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spelling pubmed-43816022015-04-09 MIG-7 and phosphorylated prohibitin coordinately regulate lung cancer invasion/metastasis Ho, Ming-Yi Liang, Chi-Ming Liang, Shu-Mei Oncotarget Research Paper Growth factors and COX-2/PGE2 enhance lung cancer invasion/metastasis via PI3K/Akt and RAS/Raf. Here, we explored their mechanism of action further. We found first that higher levels of migration inducting gene-7 protein (MIG-7) and PHB phosphorylated at threonine 258 (phospho-PHB(T258)) are positively correlated with advanced stages of human lung cancer in tissue microarray. PGE2 or growth factors such as EGF, HGF and IGF-1 increased complex formation of phospho-PHB(T258) with Ras, phospho-Akt(S473), phospho-Raf-1(S338), MEKK1 and IKKα/β(S176/180) in the raft domain transiently within 1 hour and MIG-7 in the cytosol 12-24 hours later. Association of phospho-PHB(T258) with MEKK1 but not MEKK3 activates IKK/IκB/NF-κB and MEK/ERK to increase cellular COX-2/PGE2 and an E-cadherin suppressor Snail leading to enhancement of epithelial-mesenchymal transition (EMT) and lung cancer migration/invasion. MIG-7, on the other hand, was induced by growth factors and PGE2 via Akt/GSK-3β in a phospho-PHB(T258) independent manner. MIG-7 increased two E-cadherin suppressors ZEB-1 and Twist to enhance EMT and cancer migration/invasion. Downregulating phospho-PHB(T258) and MIG-7 had an additive effect on attenuating lung cancer invasion/metastasis and prolonging the survival of xenograft mice. Phospho-PHB(T258) and MIG-7 may thus play complementary roles in the initiation and sustainment of the effects of growth factors and COX-2/PGE2 on cancer invasion/metastasis. Impact Journals LLC 2014-11-16 /pmc/articles/PMC4381602/ /pubmed/25575814 Text en Copyright: © 2015 Ho et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Ho, Ming-Yi
Liang, Chi-Ming
Liang, Shu-Mei
MIG-7 and phosphorylated prohibitin coordinately regulate lung cancer invasion/metastasis
title MIG-7 and phosphorylated prohibitin coordinately regulate lung cancer invasion/metastasis
title_full MIG-7 and phosphorylated prohibitin coordinately regulate lung cancer invasion/metastasis
title_fullStr MIG-7 and phosphorylated prohibitin coordinately regulate lung cancer invasion/metastasis
title_full_unstemmed MIG-7 and phosphorylated prohibitin coordinately regulate lung cancer invasion/metastasis
title_short MIG-7 and phosphorylated prohibitin coordinately regulate lung cancer invasion/metastasis
title_sort mig-7 and phosphorylated prohibitin coordinately regulate lung cancer invasion/metastasis
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4381602/
https://www.ncbi.nlm.nih.gov/pubmed/25575814
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