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Series GSE95536 Query DataSets for GSE95536
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
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.
 
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.
 
Contributor(s) Busch H, Börries M, Ohse S, Dvornikov D, Klingmüller U
Citation(s) 29934580
Submission date Feb 28, 2017
Last update date May 15, 2019
Contact name Hauke Busch
E-mail(s) hauke.busch@uni-luebeck.de
Phone +49-451-3101-8470
Organization name University of Lübeck
Department Lübeck Institute of Experimental Dermatology
Street address Ratzeburger Allee 160
City Lübeck
State/province Schleswig-Holstein
ZIP/Postal code 23538
Country Germany
 
Platforms (1)
GPL20301 Illumina HiSeq 4000 (Homo sapiens)
Samples (24)
GSM2516009 Control 0h a
GSM2516010 Control 0h b
GSM2516011 Control 0h c
Relations
BioProject PRJNA377341
SRA SRP100878

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Supplementary file Size Download File type/resource
GSE95536_RAW.tar 55.2 Mb (http)(custom) TAR (of TSV)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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