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Downregulation of the TGFb pseudoreceptor BAMBI in non-small cell lung cancer enhances TGFb signaling and invasion

<p>Non-small cell lung cancer (NSCLC) is characterized by early metastasis and has the highest mortality rate among all solid tumors, with the majority of patients diagnosed at an advanced stage where curative therapeutic options are lacking. In this study, we identify a targetable mechanism i...

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Main Authors: Marwitz, Sebastian (Author) , Depner, Sofia (Author) , Dvornikov, Dmytro (Author) , Merkle, Ruth (Author) , Szczygieł, Magdalena (Author) , Müller-Decker, Karin (Author) , Lucarelli, Philippe (Author) , Wäsch, Marvin (Author) , Mairbäurl, Heimo (Author) , Rabe, Klaus F. (Author) , Kügler, Christian (Author) , Vollmer, Ekkehard Karl Ludwig (Author) , Reck, Martin (Author) , Scheufele, Swetlana (Author) , Kröger, Maren (Author) , Ammerpohl, Ole (Author) , Siebert, Reiner (Author) , Goldmann, Torsten (Author) , Klingmüller, Ursula (Author)
Format: Article (Journal)
Language:English
Published: July 2016
In: Cancer research
Year: 2016, Volume: 76, Issue: 13, Pages: 3785-3801
ISSN:1538-7445
DOI:10.1158/0008-5472.CAN-15-1326
Online Access:Verlag, kostenfrei, Volltext: http://dx.doi.org/10.1158/0008-5472.CAN-15-1326
Verlag, kostenfrei, Volltext: http://cancerres.aacrjournals.org/content/76/13/3785
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Author Notes:Sebastian Marwitz, Sofia Depner, Dmytro Dvornikov, Ruth Merkle, Magdalena Szczygieł, Karin Müller-Decker, Philippe Lucarelli, Marvin Wäsch, Heimo Mairbäurl, Klaus F. Rabe, Christian Kugler, Ekkehard Vollmer, Martin Reck, Swetlana Scheufele, Maren Kröger, Ole Ammerpohl, Reiner Siebert, Torsten Goldmann, and Ursula Klingmüller
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Summary:<p>Non-small cell lung cancer (NSCLC) is characterized by early metastasis and has the highest mortality rate among all solid tumors, with the majority of patients diagnosed at an advanced stage where curative therapeutic options are lacking. In this study, we identify a targetable mechanism involving TGFβ elevation that orchestrates tumor progression in this disease. Substantial activation of this pathway was detected in human lung cancer tissues with concomitant downregulation of BAMBI, a negative regulator of the TGFβ signaling pathway. Alterations of epithelial-to-mesenchymal transition (EMT) marker expression were observed in lung cancer samples compared with tumor-free tissues. Distinct alterations in the DNA methylation of the gene regions encoding TGFβ pathway components were detected in NSCLC samples compared with tumor-free lung tissues. In particular, epigenetic silencing of BAMBI was identified as a hallmark of NSCLC. Reconstitution of BAMBI expression in NSCLC cells resulted in a marked reduction of TGFβ-induced EMT, migration, and invasion <i>in vitro</i>, along with reduced tumor burden and tumor growth <i>in vivo</i>. In conclusion, our results demonstrate how BAMBI downregulation drives the invasiveness of NSCLC, highlighting TGFβ signaling as a candidate therapeutic target in this setting. <i>Cancer Res; 76(13); 3785-801. ©2016 AACR</i>.</p>
Item Description:Gesehen am 29.01.2018
Physical Description:Online Resource
ISSN:1538-7445
DOI:10.1158/0008-5472.CAN-15-1326

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