title: HOXD3 enhances motility and invasiveness through the TGF-beta-dependent and -independent pathways in A549 cells.
abstract: Homeobox genes regulate sets of genes that determine cellular fates in embryonic morphogenesis and maintenance of adult tissue architecture by regulating cellular motility and cell-cell interactions. Our previous studies showed that a specific member, HOXD3, when overexpressed, upregulates integrin beta3 expression in human erythroleukemia HEL cells and lung cancer A549 cells, and enhances their motility and invasiveness. We performed a microarray study of over 7075 genes to determine the mechanisms underlying the HOXD3-enhanced motility and invasiveness in A549 cells. RT-PCR-based tracking gene analyses highlighted a set of TGF-beta-upregulated genes, which included matrix metalloproteinase-2, syndecan-1, CD44, and TGF-beta-induced 68 kDa protein. Exogenous TGF-beta also caused this pattern of upregulation in A549 cells and enhanced their migratory and invasive activity, confirming the involvement of TGF-beta signaling. However, HOXD3 reduced the expression of TGF-beta-independent genes coding for desmosomal components such as desmoglein, desmoplakin and plakoglobin which are known to suppress tumor invasion and metastasis. These results suggest that HOXD3 enhances the invasive and metastatic potential of cancer cells through the TGF-beta-dependent and -independent pathways.
authors.affiliation: Division of Cancer-Related Genes, Institute for Genetic Medicine, Hokkaido University, Kita-15, Nishi-7, Kita-ku, Sapporo 060-0815, Japan.
authors.forename: Yasumasa J
authors.initials: YJ
authors.lastname: Miyazaki
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Hamada
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Tada
authors.forename: Keiji
authors.initials: K
authors.lastname: Furuuchi
authors.forename: Yoko
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kondo
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Katoh
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Moriuchi
mesh_terms: D002465:Cell Movement; D004268:DNA-Binding Proteins; D015536:Down-Regulation; D020869:Gene Expression Profiling; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D015398:Signal Transduction; D014157:Transcription Factors; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
chemical_list: D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D012334:RNA, Neoplasm; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; C073547:HOXA4 protein, human