Targeting GLI1 expression in human inflammatory breast cancer cells enhances apoptosis and attenuates migration.

Published

Journal Article

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. CONCLUSION: 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.

Full Text

Duke Authors

Cited Authors

  • Thomas, ZI; Gibson, W; Sexton, JZ; Aird, KM; Ingram, SM; Aldrich, A; Lyerly, HK; Devi, GR; Williams, KP

Published Date

  • May 10, 2011

Published In

Volume / Issue

  • 104 / 10

Start / End Page

  • 1575 - 1586

PubMed ID

  • 21505458

Pubmed Central ID

  • 21505458

Electronic International Standard Serial Number (EISSN)

  • 1532-1827

Digital Object Identifier (DOI)

  • 10.1038/bjc.2011.133

Language

  • eng

Conference Location

  • England