title: ALX1 induces snail expression to promote epithelial-to-mesenchymal transition and invasion of ovarian cancer cells.
abstract: Ovarian cancer is a highly invasive and metastatic disease with a poor prognosis if diagnosed at an advanced stage, which is often the case. Recent studies argue that ovarian cancer cells that have undergone epithelial-to-mesenchymal transition (EMT) acquire aggressive malignant properties, but the relevant molecular mechanisms in this setting are not well-understood. Here, we report findings from an siRNA screen that identified the homeobox transcription factor ALX1 as a novel regulator of EMT. RNA interference-mediated attenuation of ALX1 expression restored E-cadherin expression and cell-cell junction formation in ovarian cancer cells, suppressing cell invasion, anchorage-independent growth, and tumor formation. Conversely, enforced expression of ALX1 in ovarian cancer cells or nontumorigenic epithelial cells induced EMT. We found that ALX1 upregulated expression of the key EMT regulator Snail (SNAI1) and that it mediated EMT activation and cell invasion by ALX1. Our results define the ALX1/Snail axis as a novel EMT pathway that mediates cancer invasion.
authors.affiliation: Department of Obstetrics and Gynecology and Division of Cancer Biology, Nagoya University Graduate School of Medicine, Showa, Nagoya, Japan.
authors.forename: Hong
authors.initials: H
authors.lastname: Yuan
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kajiyama
authors.forename: Satoko
authors.initials: S
authors.lastname: Ito
authors.forename: Nobuhisa
authors.initials: N
authors.lastname: Yoshikawa
authors.forename: Toshinori
authors.initials: T
authors.lastname: Hyodo
authors.forename: Eri
authors.initials: E
authors.lastname: Asano
authors.forename: Hitoki
authors.initials: H
authors.lastname: Hasegawa
authors.forename: Masao
authors.initials: M
authors.lastname: Maeda
authors.forename: Kiyosumi
authors.initials: K
authors.lastname: Shibata
authors.forename: Michinari
authors.initials: M
authors.lastname: Hamaguchi
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Kikkawa
authors.forename: Takeshi
authors.initials: T
authors.lastname: Senga
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D009361:Neoplasm Invasiveness; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D034622:RNA Interference; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C489985:ALX1 protein, human; D018398:Homeodomain Proteins; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors