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Status |
Public on Jun 15, 2018 |
Title |
Expression of TGFβ-inducible myosin-X predicts survival and chemotherapy resistance in squamous cell lung cancer |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Squamous cell lung carcinoma (SCC) corresponds to about 25% of all lung cancers. Therapeutic approaches are very limited and platinum-based chemotherapy remains the main treatment option. Despite multiple studies, there are no generally accepted predictive biomarkers for SCC. Transforming growth factor-β (TGFβ) signaling was shown to be implicated in numerous pro-tumorigenic processes, including immune evasion, inflammation and cancer metastasis. In the context of SCC epithelial-to-mesenchymal transition phenotype that is commonly mediated by TGFβ was widely observed in surgically resected specimens. However, the relation between TGFβ-induced changes and SCC progression remains to be elucidated. In the presented work, we combined phenotypic and transcriptome-wide approaches to identify novel predictive biomarkers for SCC. We show that TGFβ treatment activated Smad-mediated signal transduction and resulted in increase of migratory and invasive properties of SK-MES1 cells. Multiple actin cytoskeleton-related proteins, including myosin motor proteins such as Myosin-X, were up-regulated upon TGFβ stimulation. siRNA-mediated knockdown of Myosin-X completely abrogated TGFβ-induced collagen gel invasion. Finally, analysis of mRNA expression in paired surgically resected tissues of 151 SCC patients with corresponding 80-month clinical follow-up, showed that the mRNA expression ratio of Myosin-X in tumor and adjacent non-tumor tissue is predictive for overall survival and chemotherapy resistance independently of tumor stage. Given Myosin-X role in cellular motility and invasion, it can represent a new biomarker for aggressive disease and serve as a potential molecular target for therapeutic intervention in patients with SCC.
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Overall design |
SK-MES-1 cells were treated with TGFb or left untreated and mRNA isolated at t=[0h, 8h, 24h, 48h] in biological triplicates.
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Contributor(s) |
Busch H, Börries M, Ohse S, Dvornikov D, Klingmüller U |
Citation(s) |
29934580 |
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Submission date |
Feb 28, 2017 |
Last update date |
May 15, 2019 |
Contact name |
Hauke Busch |
E-mail(s) |
hauke.busch@uni-luebeck.de
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Phone |
+49-451-3101-8470
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Organization name |
University of Lübeck
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Department |
Lübeck Institute of Experimental Dermatology
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Street address |
Ratzeburger Allee 160
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City |
Lübeck |
State/province |
Schleswig-Holstein |
ZIP/Postal code |
23538 |
Country |
Germany |
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Platforms (1) |
GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
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Samples (24)
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Relations |
BioProject |
PRJNA377341 |
SRA |
SRP100878 |