In lung cancer a deregulation of Transforming Growth Factor-beta (TGFbeta) signaling has been observed. Yet, the impact of TGFbeta 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 TGFbeta results in an increase of migratory invasive properties. The analysis of the dynamics of gene expression by next-generation sequencing revealed that TGFbeta 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 TGFbeta-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.
- Dvornikov, D.
- Schneider, M. A.
- Ohse, S.
- Szczygiel, M.
- Titkova, I.
- Rosenblatt, M.
- Muley, T.
- Warth, A.
- Herth, F. J.
- Dienemann, H.
- Thomas, M.
- Timmer, J.
- Schilling, M.
- Busch, H.
- Boerries, M.
- Meister, M.
- Klingmuller, U.
