title: The orthologous Tbx transcription factors Omb and TBX2 induce epithelial cell migration and extrusion in vivo without involvement of matrix metalloproteinases.
abstract: The transcription factors TBX2 and TBX3 are overexpressed in various human cancers. Here, we investigated the effect of overexpressing the orthologous Tbx genes Drosophila optomotor-blind (omb) and human TBX2 in the epithelium of the Drosophila wing imaginal disc and observed two types of cell motility. Omb/TBX2 overexpressing cells could move within the plane of the epithelium. Invasive cells migrated long-distance as single cells retaining or regaining normal cell shape and apico-basal polarity in spite of attenuated apical DE-cadherin concentration. Inappropriate levels of DE-cadherin were sufficient to drive cell migration in the wing disc epithelium. Omb/TBX2 overexpression and reduced DE-cadherin-dependent adhesion caused the formation of actin-rich lateral cell protrusions. Omb/TBX2 overexpressing cells could also delaminate basally, penetrating the basal lamina, however, without degradation of extracellular matrix. Expression of Timp, an inhibitor of matrix metalloproteases, blocked neither intraepithelial motility nor basal extrusion. Our results reveal an MMP-independent mechanism of cell invasion and suggest a conserved role of Tbx2-related proteins in cell invasion and metastasis-related processes.
authors.affiliation: Department of Entomology, China Agricultural University, Beijing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Shen
authors.affiliation: Department of Entomology, China Agricultural University, Beijing, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Entomology, China Agricultural University, Beijing, China.
authors.forename: Liyuan
authors.initials: L
authors.lastname: Sui
authors.affiliation: Department of Entomology, China Agricultural University, Beijing, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.affiliation: Key Laboratory of Carbon Fiber and Functional Polymers, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing, China.
authors.forename: Meizhen
authors.initials: M
authors.lastname: Yin
authors.affiliation: Institute of Genetics, Johannes Gutenberg-University, Mainz, Germany.
authors.forename: Inka
authors.initials: I
authors.lastname: Hoffmann
authors.affiliation: Institute of Genetics, Johannes Gutenberg-University, Mainz, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Legler
authors.affiliation: Institute of Genetics, Johannes Gutenberg-University, Mainz, Germany.
authors.forename: Gert O
authors.initials: GO
authors.lastname: Pflugfelder
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002465:Cell Movement / Q000502:physiology*; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D020782:Matrix Metalloproteinases / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D009419:Nerve Tissue Proteins; C097348:T-Box Domain Protein 2; D020825:T-Box Domain Proteins; C072962:bi protein, Drosophila; D020782:Matrix Metalloproteinases