Abstract
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.
| Original language | English |
|---|---|
| Article number | 9517 |
| Journal | Scientific Reports |
| Volume | 8 |
| Issue number | 1 |
| ISSN | 2045-2322 |
| DOIs | |
| Publication status | Published - 01.12.2018 |
Funding
The support of Damir Krunic from the DKFZ Light Microscopy facility is gratefully acknowledged. Authors thank Bettina Oehrle and Gerald Burgstaller from Oliver Eickelberg’s lab at CPC Munich for their help with establishing the 3D collagen invasion assay. We would like to thank Martin Fallenbuechel, Chang Xu, Jessica Eschenbach and Christa Stolp for expert technical assistance. This study was funded by the German Center for Lung Research [Deutsches Zentrum für Lungenforschung (DZL), grant numbers 82DZL00404, 82DZL00402, 82DZL004A2]. Funding from the BMBF within the CancerSys network “LungSys II” (grant numbers 0316042A, 0316042B, 0316042D) and within the framework of the e:Med research and funding concept – DeCaRe is also acknowledged (grant number 01ZX1409B). Irina Titkova and Magdalena Szczygieł were supported by the IMOMESIC project within ERASysAPP network (grant number 031A604A), Melanie Boerries was supported by the DFG CRC 850 “Control of Cell Motility in Morphogenesis, Cancer Invasion and Metastasis” (grant number SFB/2) and Hauke Busch acknowledges support by the DFG excellence cluster 306 “Inflammation at Interfaces” (grant number EXC306). Jens Timmer and Marcus Rosenblatt were funded by MS_DILI (grant number 031L0074B).
