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Updated: Jun 2, 2026
Isolation and Functional Assessment of Human Breast Cancer Stem Cells from Cell and Tissue Samples
Published on: October 2, 2020
Targeting GLI1 expression in human inflammatory breast cancer cells enhances apoptosis and attenuates migration
Z I Thomas1, W Gibson, J Z Sexton
1Biomanufacturing Research Institute and Technology Enterprise, Durham, North Carolina Central University, Durham, NC 27707, USA.
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.
Insights
Targeting GLI1, a marker for hedgehog-pathway activation, shows promise for inflammatory breast cancer (IBC). Reducing GLI1 levels inhibited IBC cell proliferation, survival, and migration, suggesting GLI1 as a novel therapeutic target for IBC patients.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Inflammatory breast cancer (IBC) is an aggressive breast cancer subtype.
- Gene expression profiling identified the sonic hedgehog (SHH) pathway as differentially regulated in IBC.
- GLI1 is a key downstream mediator of the SHH pathway.
Purpose of the Study:
- To investigate the role of GLI1 in inflammatory breast cancer (IBC) cell proliferation, survival, and migration.
- To evaluate GLI1 as a potential therapeutic target for IBC.
Main Methods:
- Assessed GLI1 expression in IBC cell lines (SUM149, rSUM149) and a non-invasive cell line (MCF-7).
- Reduced GLI1 levels using small interfering RNA and a GLI1 inhibitor.
- Evaluated effects on cell proliferation (MTT assay), apoptosis (Annexin-V/PI assay), and migration (wound-healing and high-content assays).
Main Results:
- Elevated GLI1 expression was observed in highly invasive IBC cell lines (SUM149, rSUM149).
- GLI1 downregulation decreased proliferation and increased apoptosis in SUM149 and rSUM149 cells.
- GLI1 suppression significantly inhibited cell migration in IBC cell lines compared to MCF-7 cells.
Conclusions:
- GLI1 plays a significant role in the proliferation, survival, and migration of IBC cells.
- Targeting GLI1 represents a feasible and novel therapeutic strategy for inflammatory breast cancer patients.
