title: Targeting GLI1 expression in human inflammatory breast cancer cells enhances apoptosis and attenuates migration.
abstract: BACKGROUND
  Inflammatory breast cancer (IBC) is an aggressive subtype of breast cancer with distinct molecular profiles. Gene expression profiling previously identified sonic hedgehog (SHH) as part of a gene signature that is differentially regulated in IBC patients.
  
  
  METHODS
  The effects of reducing GLI1 levels on protein expression, cell proliferation, apoptosis and migration were determined by immunoblots, MTT assay, Annexin-V/PI assay and conventional and automated cell migration assays.
  
  
  RESULTS
  Evaluation of a panel of breast cancer cell lines revealed elevated GLI1 expression, typically a marker for hedgehog-pathway activation, in a triple-negative, highly invasive IBC cell line, SUM149 and its isogenic-derived counterpart rSUM149 that has acquired resistance to ErbB1/2 targeting strategies. Downregulation of GLI1 expression in SUM149 and rSUM149 by small interfering RNA or a small molecule GLI1 inhibitor resulted in decreased proliferation and increased apoptosis. Further, GLI1 suppression in these cell lines significantly inhibited cell migration as assessed by a wound-healing assay compared with MCF-7, a non-invasive cell line with low GLI1 expression. A novel high-content migration assay allowed us to quantify multiple effects of GLI1 silencing including significant decreases in cell distance travelled and linearity of movement.
  
  
  CONCLUSIONS
  Our data reveal a role for GLI1 in IBC cell proliferation, survival and migration, which supports the feasibility of targeting GLI1 as a novel therapeutic strategy for IBC patients.
authors.affiliation: Biomanufacturing Research Institute and Technology Enterprise, Durham, North Carolina Central University, Durham, NC 27707, USA.
authors.forename: Z I
authors.initials: ZI
authors.lastname: Thomas
authors.forename: W
authors.initials: W
authors.lastname: Gibson
authors.forename: J Z
authors.initials: JZ
authors.lastname: Sexton
authors.forename: K M
authors.initials: KM
authors.lastname: Aird
authors.forename: S M
authors.initials: SM
authors.lastname: Ingram
authors.forename: A
authors.initials: A
authors.lastname: Aldrich
authors.forename: H K
authors.initials: HK
authors.lastname: Lyerly
authors.forename: G R
authors.initials: GR
authors.lastname: Devi
authors.forename: K P
authors.initials: KP
authors.lastname: Williams
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D048708:Cell Growth Processes / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D058922:Inflammatory Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D058990:Molecular Targeted Therapy / Q000379:methods; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics; D000071676:Zinc Finger Protein GLI1
chemical_list: C400551:GLI1 protein, human; D034741:RNA, Small Interfering; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1