Cited 6 time in webofscience Cited 5 time in scopus

Chronic TGF beta stimulation promotes the metastatic potential of lung cancer cells by Snail protein stabilization through integrin beta 3-Akt-GSK3 beta signaling

Title
Chronic TGF beta stimulation promotes the metastatic potential of lung cancer cells by Snail protein stabilization through integrin beta 3-Akt-GSK3 beta signaling
Authors
Bae, GY[Bae, Gab-Yong]Hong, SK[Hong, Soon-Ki]Park, JR[Park, Jeong-Rak]Kwon, OS[Kwon, Ok-Seon]Kim, KT[Kim, Keun-Tae]Koo, J[Koo, JaeHyung]Oh, E[Oh, Ensel]Cha, HJ[Cha, Hyuk-Jin]
DGIST Authors
Koo, J[Koo, JaeHyung]
Issue Date
2016-05-03
Citation
Oncotarget, 7(18), 25366-25376
Type
Article
Article Type
Article
Keywords
A549 Cell LineAKTBeta3 IntegrinCancer PrognosisCell InvasionCell MigrationChronic TGF Beta ExposureControlled StudyGene ExpressionGlycogen Synthase Kinase-3BetaGSK-3 BetaHumanIntegrin Beta 3Long Term ExposureLung AdenocarcinomaLung Cancer Cell LineMajor Clinical StudyMessenger RNAMetastasis PotentialOverall SurvivalProtein Kinase BProtein PhosphorylationProtein StabilitySignal TransductionSmad ProteinSnailTranscription Factor SnailTransforming Growth Factor Beta
ISSN
1949-2553
Abstract
Chronic exposure to TGFβ, a frequent occurrence for tumor cells in the tumor microenvironment, confers more aggressive phenotypes on cancer cells by promoting their invasion and migration while at the same time increasing their resistance to the growth-inhibitory effect of TGFβ. In this study, a transdifferentiated (TD) A549 cell model, established by chronically exposing A549 cells to TGFβ, showed highly invasive phenotypes in conjunction with attenuation of Smad-dependent signaling. We show that Snail protein, the mRNA expression of which strongly correlates with a poor prognosis in lung cancer patients, was highly stable in TD cells after TGFβ stimulation. The increased protein stability of Snail in TD cells correlated with elevated inhibitory phosphorylation of GSK3β, resulting from the high Akt activity. Notably, integrin β3, whose expression was markedly increased upon sustained exposure to TGFβ, was responsible for the high Akt activity as well as the increased Snail protein stability in TD cells. Consistently, clinical database analysis on lung cancer patients revealed a negative correlation between overall survival and integrin β3 mRNA levels. Therefore, we suggest that the integrin β3-Akt-GSK3β signaling axis plays an important role in non-canonical TGFβ signaling, determining the invasive properties of tumor cells chronically exposed to TGFβ.
URI
http://hdl.handle.net/20.500.11750/2541
DOI
10.18632/oncotarget.8295
Publisher
Impact Journals LLC
Related Researcher
  • Author Koo, Jae Hyung The Koo Lab - ChemoReception Laboratory(CRLab)
  • Research Interests
Files:
There are no files associated with this item.
Collection:
New BiologyETC1. Journal Articles


qrcode mendeley

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE