title: SATB2 enhances migration and invasion in osteosarcoma by regulating genes involved in cytoskeletal organization.
abstract: Osteosarcoma (OS) is the most common malignant bone tumor and the majority of recurrences are due to metastasis. However, the molecular mechanisms that regulate OS metastatic spread are largely unknown. In this study, we report that special AT-rich-binding protein 2 (SATB2) is highly expressed in OS cells and tumors. Short hairpin RNA-mediated knockdown of SATB2 (sh-SATB2) decreases migration and invasion of OS cells without affecting proliferation or viability. Microarray analysis identified genes that were differentially regulated by SATB2 including the actin-binding protein Epithelial Protein Lost In Neoplasm (EPLIN), which was upregulated in sh-SATB2 cells. Silencing EPLIN rescues the decreased invasion observed in sh-SATB2 cells. Pathway analyses of SATB2-regulated genes revealed enrichment of those involved in cytoskeleton dynamics, and increased stress fiber formation was detected in cells with SATB2 knockdown. Furthermore, sh-SATB2 cells exhibit increased RhoA, decreased Rac1 and increased phosphorylation of focal adhesion kinase (FAK) and paxillin. These findings identify SATB2 as a novel regulator of OS invasion, in part via effects on EPLIN and the cytoskeleton.
authors.affiliation: 1] Departments of Pediatrics and Medical Biophysics, University of Toronto, Toronto, Ontario, Canada [2] Cell Biology Program, Hospital for Sick Children Research Institute, Peter Gilgan Centre for Research and Learning, Toronto, Ontario, Canada.
authors.forename: B K A
authors.initials: BK
authors.lastname: Seong
authors.affiliation: Cell Biology Program, Hospital for Sick Children Research Institute, Peter Gilgan Centre for Research and Learning, Toronto, Ontario, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Lau
authors.affiliation: Cell Biology Program, Hospital for Sick Children Research Institute, Peter Gilgan Centre for Research and Learning, Toronto, Ontario, Canada.
authors.forename: T
authors.initials: T
authors.lastname: Adderley
authors.affiliation: Cell Biology Program, Hospital for Sick Children Research Institute, Peter Gilgan Centre for Research and Learning, Toronto, Ontario, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Kee
authors.affiliation: Cell Biology Program, Hospital for Sick Children Research Institute, Peter Gilgan Centre for Research and Learning, Toronto, Ontario, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Chaukos
authors.affiliation: Program in Genetics and Genome Biology, Hospital for Sick Children Research Institute, Peter Gilgan Centre for Research and Learning, Toronto, Ontario, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Pienkowska
authors.affiliation: 1] Departments of Pediatrics and Medical Biophysics, University of Toronto, Toronto, Ontario, Canada [2] Program in Genetics and Genome Biology, Hospital for Sick Children Research Institute, Peter Gilgan Centre for Research and Learning, Toronto, Ontario, Canada [3] Division of Hematology-Oncology, Department of Pediatrics, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Malkin
authors.affiliation: 1] Department of Pediatric Laboratory Medicine, Hospital for Sick Children, Toronto, Ontario, Canada [2] Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: P
authors.initials: P
authors.lastname: Thorner
authors.affiliation: 1] Departments of Pediatrics and Medical Biophysics, University of Toronto, Toronto, Ontario, Canada [2] Cell Biology Program, Hospital for Sick Children Research Institute, Peter Gilgan Centre for Research and Learning, Toronto, Ontario, Canada [3] Division of Hematology-Oncology, Department of Pediatrics, Hospital for Sick Children, Toronto, Ontario, Canada [4] Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: M S
authors.initials: MS
authors.lastname: Irwin
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement / Q000235:genetics*; D003598:Cytoskeletal Proteins / Q000235:genetics; D003599:Cytoskeleton / Q000235:genetics* / Q000378:metabolism*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D036961:Matrix Attachment Region Binding Proteins / Q000502:physiology*; D051379:Mice; D046228:Microarray Analysis; D009361:Neoplasm Invasiveness; D012516:Osteosarcoma / Q000235:genetics / Q000473:pathology*; D014157:Transcription Factors / Q000502:physiology*; D014407:Tumor Cells, Cultured
chemical_list: D003598:Cytoskeletal Proteins; C403263:LIMA1 protein, human; D036961:Matrix Attachment Region Binding Proteins; C521297:SATB2 protein, human; D014157:Transcription Factors