Downregulation of the TGFβ Pseudoreceptor BAMBI in Non–Small Cell Lung Cancer Enhances TGFβ Signaling and Invasion
| العنوان: | Downregulation of the TGFβ Pseudoreceptor BAMBI in Non–Small Cell Lung Cancer Enhances TGFβ Signaling and Invasion |
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| المؤلفون: | Martin Reck, Heimo Mairbäurl, Karin Müller-Decker, Marvin Wäsch, Torsten Goldmann, Ekkehard Vollmer, Reiner Siebert, Swetlana Scheufele, Sofia Depner, Ruth Merkle, Ole Ammerpohl, Magdalena Szczygiel, Sebastian Marwitz, Philippe Lucarelli, Maren Kröger, Christian Kugler, Ursula Klingmüller, Dmytro Dvornikov, Klaus F. Rabe |
| المصدر: | Cancer Research. 76:3785-3801 |
| بيانات النشر: | American Association for Cancer Research (AACR), 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Cancer Research, Pathology, Lung Neoplasms, Fluorescent Antibody Technique, Apoptosis, Epigenesis, Genetic, Metastasis, Immunoenzyme Techniques, Mice, 0302 clinical medicine, Cell Movement, Transforming Growth Factor beta, Carcinoma, Non-Small-Cell Lung, Tumor Cells, Cultured, biology, Reverse Transcriptase Polymerase Chain Reaction, Prognosis, Oncology, 030220 oncology & carcinogenesis, Carcinoma, Squamous Cell, Female, Signal Transduction, medicine.medical_specialty, Epithelial-Mesenchymal Transition, Blotting, Western, Down-Regulation, Mice, Nude, Adenocarcinoma, Real-Time Polymerase Chain Reaction, 03 medical and health sciences, Downregulation and upregulation, Biomarkers, Tumor, medicine, Animals, Humans, Neoplasm Invasiveness, RNA, Messenger, Epithelial–mesenchymal transition, Lung cancer, Aged, Cell Proliferation, Neoplasm Staging, Membrane Proteins, Cancer, Transforming growth factor beta, DNA Methylation, medicine.disease, Xenograft Model Antitumor Assays, respiratory tract diseases, 030104 developmental biology, Tumor progression, Case-Control Studies, biology.protein, Cancer research, BAMBI, Follow-Up Studies |
| الوصف: | 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 in vitro, along with reduced tumor burden and tumor growth in vivo. In conclusion, our results demonstrate how BAMBI downregulation drives the invasiveness of NSCLC, highlighting TGFβ signaling as a candidate therapeutic target in this setting. Cancer Res; 76(13); 3785–801. ©2016 AACR. |
| تدمد: | 1538-7445 0008-5472 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::769d16733fd91ff57cdd560a476c8d8b https://doi.org/10.1158/0008-5472.can-15-1326 |
| رقم الأكسشن: | edsair.doi.dedup.....769d16733fd91ff57cdd560a476c8d8b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15387445 00085472 |
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