title: Jun-regulated genes promote interaction of diffuse large B-cell lymphoma with the microenvironment.
abstract: Diffuse large B-cell lymphoma (DLBCL) is an aggressive disease with a high proliferation rate. However, the molecular and genetic features that drive the aggressive clinical behavior of DLBCL are not fully defined. Here, we have demonstrated that activated Jun signaling is a frequent event in DLBCL that promotes dissemination of malignant cells. Downregulation of Jun dramatically reduces lymphoma cell adhesion to extracellular matrix proteins, subcutaneous tumor size in nude mice, and invasive behavior, including bone marrow infiltration and interaction with bone marrow stromal cells. Furthermore, using a combination of RNA interference and gene expression profiling, we identified Jun target genes that are associated with disseminated lymphoma. Among them, ITGAV, FoxC1, and CX3CR1 are significantly enriched in patients with 2 or more extranodal sites. Our results point to activated Jun signaling as a major driver of the aggressive phenotype of DLBCL.
authors.affiliation: Department of Molecular and Cellular Oncology, Center for Inflammation and Cancer.
authors.forename: Marzenna
authors.initials: M
authors.lastname: Blonska
authors.affiliation: Department of Molecular and Cellular Oncology.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Nuclear Medicine, and.
authors.forename: Hubert H
authors.initials: HH
authors.lastname: Chuang
authors.affiliation: Center for Inflammation and Cancer, Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX;
authors.forename: M James
authors.initials: MJ
authors.lastname: You
authors.affiliation: Department of Pathology, Sylvester Cancer Center, University of Miami, Miami, FL; and.
authors.forename: Kranthi
authors.initials: K
authors.lastname: Kunkalla
authors.affiliation: Department of Pathology, Sylvester Cancer Center, University of Miami, Miami, FL; and.
authors.forename: Francisco
authors.initials: F
authors.lastname: Vega
authors.affiliation: Department of Molecular and Cellular Oncology, Center for Inflammation and Cancer, Cancer Biology Program, The University of Texas Graduate School of Biomedical Sciences, Houston, TX.
authors.forename: Xin
authors.initials: X
authors.lastname: Lin
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D008819:Mice, Nude; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D016326:Extracellular Matrix Proteins; C584097:JunB protein, mouse; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; D014157:Transcription Factors