Caveolin-1 promotes Ewing sarcoma metastasis regulating MMP-9 expression through MAPK/ERK pathway

• DOI: 10.18632/oncotarget.10872
• Publication Date: 2016-07-28T14:43:28Z
• Authors: Laura Lagares-Tena; Silvia García-Mon...; Roser López-Alemany; Olga Almacellas-R...; Juan Huertas-Mart...; Miguel Sáinz-Jasp...; Silvia Mateo-Lozano; Carlos Rodríguez-...; Santiago Rello-Va...; David Herrero-Martín; Oscar M. Tirado
• Keywords: 0301 basic medicine; caveolin-1; Oncogene Proteins, Fusion; MAP Kinase Signaling System; Caveolin 1; 610; Mice, Nude; Mice; 03 medical and health sciences; Cell Movement; Cell Line, Tumor; metastasis; Animals; Humans; Neoplasm Invasiveness; Gene Silencing; Neoplasm Metastasis; Phosphorylation; mapk; Mice, Inbred BALB C; Ribosomal Protein S6; Proto-Oncogene Protein c-fli-1; Extracellular Matrix; 3. Good health; Matrix Metalloproteinase 9; mmp9; Female; RNA-Binding Protein EWS; Ewing sarcoma; Research Paper

// Laura Lagares-Tena 1 , Silvia García-Monclús Roser López-Alemany Olga Almacellas-Rabaiget Juan Huertas-Martínez Miguel Sáinz-Jaspeado Mateo-Lozano 2 Carlos Rodríguez-Galindo 3 Santiago Rello-Varona David Herrero-Martín Oscar M. Tirado Sarcoma Research Group, Institut d’Investigació Biomèdica de Bellvitge-IDIBELL, L’Hospitalet Llobregat, Barcelona, Spain Developmental Tumor Biology Laboratory, Hospital Sant Joan Deu, Pediatric Hematology/Oncology, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Boston, Massachusetts, USA Correspondence to: Tirado, email: [e-mail] Keywords: caveolin-1, Ewing sarcoma, metastasis, mmp9, mapk Received: December 22, 2015      Accepted: July 18, 2016      Published: 28, 2016 ABSTRACT sarcoma (ES) is a bone soft tissue affecting mostly children young adults. Caveolin-1 (CAV1) well-known target of EWS/FLI1, the main driver ES, with an oncogenic role in ES. We have previously described how CAV1 able to induce metastasis ES via matrix metalloproteinase-9 (MMP-9). In present study we showed silencing reduced MEK1/2 ERK1/2 phosphorylation. Accordingly, chemical inhibition resulted reduction MMP-9 expression activity that correlated migration invasion. IQ Motif Containing GTPase Activating Protein (IQGAP1) phosphorylation expression. Furthermore, IQGAP1 silenced cells marked decrease their migratory invasive capacity. demonstrated localize close proximity at cellular edge, thus could be connecting node between MEK/ERK metastatic phenotype. Analysis profile CAV1-silenced p-ribosomal protein S6 (RPS6). RPS6 can phosphorylated by p90 ribosomal kinases (RSK) proteins. levels p-RSK1 treatment U0126 provoked same effect. Despite not status neither nor activity, RSK1 capacity vitro incidence metastases vivo novel orthotopic model. The work provides new insights into CAV1-driven process unveiling key nodes.