Serum and Glucocorticoid Inducible Kinase 1-Sensitive Survival, Proliferation and Migration of Rhabdomyosarcoma Cells

Evi Schmid, Matias Julian Stagno, Jing Yan, Sabine Schleicher, Willi Yu, Sabina Honisch, Florian Lang, Jörg Fuchs, Guido Seitz
2017 Cellular Physiology and Biochemistry  
Background/Aims: Rhabdomyosarcoma, the most common pediatric soft tissue sarcoma, may show an intrinsic refractoriness to standard chemotherapy in advanced tumor stages, which is associated with poor prognosis. Cellular mechanisms conferring tumor cell survival and therapy resistance in many tumor types include the serum & glucocorticoid inducible kinase (SGK) 1 pathway, a kinase expressed ubiquitously with particularly strong expression in skeletal muscle and some tumor types. The present
more » ... s. The present study explored whether SGK1 is expressed in rhabdomyosarcoma and, if so, whether this kinase impacts on tumor cell survival, proliferation and migration. Multiple in vitro techniques were used to study the role of SGK1 in rhabdomyosarcoma. Methods: The Gene Chip® Human Genome U133 Plus 2.0 Array were employed to examine SGK1 transcriptional activity in healthy muscle and rhabdomyosarcoma tissue. SGK1 transcript levels were quantified in rhabdomyosarcoma cell lines RD (embryonal subtype) and RH30 (alveolar subtype) by RT-PCR, cell viability was measured using MTT assays. Clonal cell growth was assessed via colony forming assays and migration experiments were performed in a transwell system. Results: SGK1 is expressed in embryonal and alveolar rhabdomyosarcoma tissue samples and in RD and RH30 rhabdomyosarcoma cell lines. Administration of EMD638683 -an inhibitor specific for SGK1decreased viability of RD and RH30 cells, enhanced the effects of the cytotoxic drug doxorubicin leading to reduced migration and decreased cell proliferation. Conclusions: SGK1 is expressed in rhabdomyosarcoma cells where it contributes to survival, therapy resistance, cell proliferation and migration. Thus, SGK1 inhibitors may be considered a therapeutic option for the treatment of therapy-resistant rhabdomyosarcoma. E. Schmid and M.J. Stagno authors contributed equally and thus share first authorship. Results The present study addressed expression and functional significance of SGK1 in rhabdomyosarcoma cells. SGK1 transcription levels were determined in muscle tissue, alveolar (RMA) and embryonal (RME) rhabdomyosarcoma tumors. As illustrated in Fig. 1A , the SGK1 mRNA expression was significantly higher in alveolar rhabdomyosarcoma tissue
doi:10.1159/000481842 pmid:28992614 fatcat:2zrqnvzoxndnzhrthtwdfpx4iy