title: The miR-199a/Brm/EGR1 axis is a determinant of anchorage-independent growth in epithelial tumor cell lines.
abstract: In epithelial cells, miRNA-199a-5p/-3p and Brm, a catalytic subunit of the SWI/SNF complex were previously shown to form a double-negative feedback loop through EGR1, by which human cancer cell lines tend to fall into either of the steady states, types 1 [miR-199a(-)/Brm(+)/EGR1(-)] and 2 [miR-199a(+)/Brm (-)/EGR1(+)]. We show here, that type 2 cells, unlike type 1, failed to form colonies in soft agar, and that CD44, MET, CAV1 and CAV2 (miR-199a targets), all of which function as plasma membrane sensors and can co-localize in caveolae, are expressed specifically in type 1 cells. Single knockdown of any of them suppressed anchorage-independent growth of type 1 cells, indicating that the miR-199a/Brm/EGR1 axis is a determinant of anchorage-independent growth. Importantly, two coherent feedforward loops are integrated into this axis, supporting the robustness of type 1-specific gene expression and exemplifying how the miRNA-target gene relationship can be stably sustained in a variety of epithelial tumors.
authors: Division of Host-Parasite Interaction, Department of Microbiology and Immunology, University of Tokyo, Tokyo, Japan.
authors: Kazuyoshi
authors: K
authors: Kobayashi
authors: Division of Host-Parasite Interaction, Department of Microbiology and Immunology, University of Tokyo, Tokyo, Japan.
authors: Kouhei
authors: K
authors: Sakurai
authors: Division of Host-Parasite Interaction, Department of Microbiology and Immunology, University of Tokyo, Tokyo, Japan.
authors: Hiroaki
authors: H
authors: Hiramatsu
authors: First Department of Pathology, Faculty of Medicine, Fujita Health University, Aichi, Japan.
authors: Ken-ichi
authors: K
authors: Inada
authors: First Department of Pathology, Faculty of Medicine, Fujita Health University, Aichi, Japan.
authors: Kazuya
authors: K
authors: Shiogama
authors: Division of Host-Parasite Interaction, Department of Microbiology and Immunology, University of Tokyo, Tokyo, Japan.
authors: Shinya
authors: S
authors: Nakamura
authors: Division of Host-Parasite Interaction, Department of Microbiology and Immunology, University of Tokyo, Tokyo, Japan.
authors: Fumiko
authors: F
authors: Suemasa
authors: Division of Host-Parasite Interaction, Department of Microbiology and Immunology, University of Tokyo, Tokyo, Japan.
authors: Kyosuke
authors: K
authors: Kobayashi
authors: Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
authors: Seiya
authors: S
authors: Imoto
authors: Division of Host-Parasite Interaction, Department of Microbiology and Immunology, University of Tokyo, Tokyo, Japan.
authors: Takeshi
authors: T
authors: Haraguchi
authors: Division of Host-Parasite Interaction, Department of Microbiology and Immunology, University of Tokyo, Tokyo, Japan.
authors: Hiroaki
authors: H
authors: Ito
authors: Division of Host-Parasite Interaction, Department of Microbiology and Immunology, University of Tokyo, Tokyo, Japan.
authors: Aya
authors: A
authors: Ishizaka
authors: First Department of Pathology, Faculty of Medicine, Fujita Health University, Aichi, Japan.
authors: Yutaka
authors: Y
authors: Tsutsumi
authors: Division of Host-Parasite Interaction, Department of Microbiology and Immunology, University of Tokyo, Tokyo, Japan.
authors: Hideo
authors: H
authors: Iba
mesh_terms: D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism; D051243:Caveolin 2 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D051766:Early Growth Response Protein 1 / Q000235:genetics*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics*; D008954:Models, Biological; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C495540:CAV1 protein, human; C495544:CAV2 protein, human; D051242:Caveolin 1; D051243:Caveolin 2; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D018960:Hyaluronan Receptors; D035683:MicroRNAs; C084011:SMARCA2 protein, human; D014157:Transcription Factors; C531408:mirn199 microRNA, human; D019859:Proto-Oncogene Proteins c-met