Gremlin-1 associates with fibrillin microfibrils in vivo and regulates mesothelioma cell survival through transcription factor slug

• DOI: 10.1038/oncsis.2013.29
• Publication Date: 2013-08-26T13:18:23Z
• Authors: J A Tamminen; V Parviainen; M Rönty; A P Wohl; L Murray; S Joenväärä; M Varjosalo; O Leppäranta; O Ritvos; G Sengle; R Renkonen; M Myllärniemi; K Koli
• Keywords: 0301 basic medicine; Cancer Research; 0303 health sciences; 03 medical and health sciences; 616; Original Article; Molecular Biology; 3. Good health

Malignant mesothelioma is a form of cancer that highly resistant to conventional therapy for which no major therapeutic advances have been introduced. Here, we identify gremlin-1, known bone morphogenetic protein inhibitor crucial embryonic development, as potential target mesothelioma. We found high expression levels gremlin-1 in the tumor tissue, well primary cells cultured from pleural effusion samples. Downregulation by siRNA-mediated silencing cell line inhibited proliferation. This was associated with downregulation transcription factor slug mesenchymal proteins linked epithelial-to-mesenchymal transition. Further, resistance paclitaxel-induced death and expression. Treatment gremlin-1-silenced paclitaxel or pemetrexed resulted efficient loss survival. Finally, our data suggest concomitant upregulation fibrillin-2 provides mechanism extracellular localization microenvironment. supported demonstration interactions between fibrillin-1 -2 peptides colocalization fibrillin microfibrils tissue Our also overcoming drug