Expression ratio of the TGFβ-inducible gene MYO10 is prognostic for overall survival of squamous cell lung cancer patients and predicts chemotherapy response

In lung cancer a deregulation of Transforming Growth Factor-β (TGFβ) signaling has been observed. Yet, the impact of TGFβ in squamous cell carcinoma of the lung (LUSC) remained to be determined. We combined phenotypic and transcriptome-wide studies and showed that the stimulation of the LUSC cell li...

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Hauptverfasser: Dvornikov, Dmytro (VerfasserIn) , Schneider, Marc (VerfasserIn) , Szczygieł, Magdalena (VerfasserIn) , Titkova, Irina (VerfasserIn) , Muley, Thomas (VerfasserIn) , Warth, Arne (VerfasserIn) , Herth, Felix (VerfasserIn) , Dienemann, Hendrik (VerfasserIn) , Thomas, Michael (VerfasserIn) , Meister, Michael (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 22 June 2018
In: Scientific reports
Year: 2018, Jahrgang: 8
ISSN:2045-2322
DOI:10.1038/s41598-018-27912-1
Online-Zugang:Verlag, Volltext: https://doi.org/10.1038/s41598-018-27912-1
Verlag, Volltext: https://www.nature.com/articles/s41598-018-27912-1
Volltext
Verfasserangaben:D. Dvornikov, M.A. Schneider, S. Ohse, M. Szczygieł, I. Titkova, M. Rosenblatt, T. Muley, A. Warth, F.J. Herth, H. Dienemann, M. Thomas, J. Timmer, M. Schilling, H. Busch, M. Boerries, M. Meister & U. Klingmüller
Beschreibung
Zusammenfassung:In lung cancer a deregulation of Transforming Growth Factor-β (TGFβ) signaling has been observed. Yet, the impact of TGFβ in squamous cell carcinoma of the lung (LUSC) remained to be determined. We combined phenotypic and transcriptome-wide studies and showed that the stimulation of the LUSC cell line SK-MES1 with TGFβ results in an increase of migratory invasive properties. The analysis of the dynamics of gene expression by next-generation sequencing revealed that TGFβ stimulation orchestrates the upregulation of numerous motility- and actin cytoskeleton-related genes. Among these the non-muscle myosin 10 (MYO10) showed the highest upregulation in a LUSC patient cohort of the Cancer Genome Atlas (TCGA). Knockdown of MYO10 abrogated TGFβ-induced collagen gel invasion of SK-MES1 cells. The analysis of MYO10 mRNA expression in paired tissues of 151 LUSC patients with corresponding 80-month clinical follow-up data showed that the mRNA expression ratio of MYO10 in tumor and tumor-free tissue is prognostic for overall survival of LUSC patients and predictive for the response of these patients to adjuvant chemotherapy. Thus, MYO10 represents a new clinical biomarker for this aggressive disease and due to its role in cellular motility and invasion could serve as a potential molecular target for therapeutic interventions in patients with LUSC.
Beschreibung:Gesehen am 09.07.2019
Beschreibung:Online Resource
ISSN:2045-2322
DOI:10.1038/s41598-018-27912-1