Thyroid Transcription Factor 1 Reprograms Angiogenic Activities of Secretome

Scientific Reports
Lauren W WoodDavid Mu

Abstract

Through both gain- and loss-of-TTF-1 expression strategies, we show that TTF-1 positively regulates vascular endothelial growth factor (VEGF) and that the VEGF promoter element contains multiple TTF-1-responsive sequences. The major signaling receptor for VEGF, i.e VEGFR2, also appears to be under a direct and positive regulation of TTF-1. The TTF-1-dependent upregulation of VEGF was moderately sensitive to rapamycin, implicating a partial involvement of mammalian target of rapamycin (mTOR). However, hypoxia did not further increase the secreted VEGF level of the TTF-1(+) lung cancer cells. The TTF-1-induced VEGF upregulation occurs in both compartments (exosomes and exosome-depleted media (EDM)) of the conditioned media. Surprisingly, the EDM of TTF-1(+) lung cancer cells (designated EDM-TTF-1(+)) displayed an anti-angiogenic activity in the endothelial cell tube formation assay. Mechanistic studies suggest that the increased granulocyte-macrophage colony-stimulating factor (GM-CSF) level in the EDM-TTF-1(+) conferred the antiangiogenic activities. In human lung cancer, the expression of TTF-1 and GM-CSF exhibits a statistically significant and positive correlation. In summary, this study provides evidence that TTF-1 may repro...Continue Reading

References

Oct 1, 1995·American Journal of Respiratory Cell and Molecular Biology·W M ManiscalcoM H Campbell
Sep 1, 1996·Molecular and Cellular Biology·J A ForsytheG L Semenza
Dec 1, 1996·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·F PezzellaA L Harris
Mar 31, 1998·Developmental Dynamics : an Official Publication of the American Association of Anatomists·X ZengJ A Whitsett
Mar 8, 2000·Developmental Dynamics : an Official Publication of the American Association of Anatomists·B YuanP Minoo
Jun 5, 2003·Nature Medicine·Napoleone FerraraJennifer LeCouter
Sep 6, 2003·Cancer Cell·James B BrugarolasWilliam G Kaelin
Sep 19, 2006·Annals of Oncology : Official Journal of the European Society for Medical Oncology·T BerghmansJ-P Sculier
Jan 24, 2007·Physiological Reviews·Yutaka MaedaJeffrey A Whitsett
May 10, 2007·Nature Protocols·Woodring E Wright, Jerry W Shay
Jul 10, 2007·Cancer Research·Hisaaki TanakaTakashi Takahashi
Oct 11, 2007·Proceedings of the National Academy of Sciences of the United States of America·Jude KendallDavid Mu
Nov 6, 2007·Nature·Barbara A WeirMatthew Meyerson
Jul 22, 2008·Nature Medicine·UNKNOWN Director's Challenge Consortium for the Molecular Classification of Lung AdenocarcinomaDavid G Beer
Dec 2, 2008·Journal of Cellular and Molecular Medicine·Justine A BarlettaLucian R Chirieac
Jan 22, 2011·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·William D TravisDavid Yankelewitz
Apr 8, 2011·Nature·Monte M WinslowTyler Jacks
Oct 13, 2011·Nucleic Acids Research·Suresh MathivananRichard J Simpson
Mar 7, 2012·The Journal of Experimental Medicine·Petra HamerlikJiri Bartek
Mar 15, 2012·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Saravanan S Karuppagounder, Rajiv R Ratan
Jul 5, 2012·The Journal of Biological Chemistry·E Aaron RunkleDavid Mu
Aug 30, 2012·Nature Methods·Caroline A SchneiderKevin W Eliceiri
Nov 13, 2012·The Journal of Clinical Investigation·Yutaka MaedaJeffrey A Whitsett
Jan 30, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Hao TangYang Xie
Mar 5, 2013·The Journal of Clinical Investigation·Sampurna ChatterjeeRoland T Ullrich
Mar 26, 2013·Molecular Cell·Eric L SnyderTyler Jacks
Nov 23, 2013·Nature Reviews. Cancer·Hira Lal Goel, Arthur M Mercurio
Apr 17, 2014·Cancer Cell·Weiying ZhouShizhen Emily Wang
Oct 16, 2014·Journal of Extracellular Vesicles·Jan Van DeunAn Hendrix

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Datasets Mentioned

BETA
GSE42127

Methods Mentioned

BETA
ELISA
antibody array
ChIP-seq
antibody
transfectant
transfecting
transfections
PCR
X-ray
transfection

Software Mentioned

Partek GS
ImageJ

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