Document Type

Article

Publication Date

12-1-2016

Keywords

Cell Line, Tumor, DNA-Binding Proteins, Epithelial-Mesenchymal Transition, Female, Gene Knockdown Techniques, Heat Shock Transcription Factors, Humans, Neoplasm Proteins, Ovarian Neoplasms, Spheroids, Cellular, Transcription Factors, Transforming Growth Factor beta

Digital Object Identifier (DOI)

https://doi.org/10.1371/journal.pone.0168389

Abstract

Ovarian cancer is the most lethal gynecological cancer, with over 200,000 women diagnosed each year and over half of those cases leading to death. The proteotoxic stress-responsive transcription factor HSF1 is frequently overexpressed in a variety of cancers and is vital to cellular proliferation and invasion in some cancers. Upon analysis of various patient data sets, we find that HSF1 is frequently overexpressed in ovarian tumor samples. In order to determine the role of HSF1 in ovarian cancer, inducible HSF1 knockdown cell lines were created. Knockdown of HSF1 in SKOV3 and HEY ovarian cancer cell lines attenuates the epithelial-to-mesenchymal transition (EMT) in cells treated with TGFβ, as determined by western blot and quantitative RT-PCR analysis of multiple EMT markers. To further explore the role of HSF1 in ovarian cancer EMT, we cultured multicellular spheroids in a non-adherent environment to simulate early avascular tumors. In the spheroid model, cells more readily undergo EMT; however, EMT inhibition by HSF1 becomes more pronounced in the spheroid model. These findings suggest that HSF1 is important in the ovarian cancer TGFβ response and in EMT.

Rights Information

Creative Commons License
This work is licensed under a Creative Commons Attribution 3.0 License.

Was this content written or created while at USF?

Yes

Citation / Publisher Attribution

PLoS ONE, v. 11, issue 12, art. e0168389

1 fig1.PNG (775 kB)
Fig 1. HSF1 levels are elevated in ovarian cancer patient samples.

1 fig 2.PNG (2134 kB)
Fig 2. Validation of inducible HSF1 knockdown ovarian cancer cell lines.

1 fig 3.PNG (3038 kB)
Fig 3. HSF1 knockdown reduces colony formation.

1 fig 4.PNG (2920 kB)
Fig 4. HSF1 knockdown inhibits wound healing, migration and induction of fibronectin.

1 fig 5.PNG (142 kB)
Fig 5. Fibronectin expression is induced by 3D growth.

1 fig 6.PNG (1736 kB)
Fig 6. TGFβ induction of EMT master-switch transcription factors are reduced upon HSF1 knockdown, and the effect is enhanced upon 3D culturing

Additional Files

1 fig1.PNG (775 kB)
Fig 1. HSF1 levels are elevated in ovarian cancer patient samples.

1 fig 2.PNG (2134 kB)
Fig 2. Validation of inducible HSF1 knockdown ovarian cancer cell lines.

1 fig 3.PNG (3038 kB)
Fig 3. HSF1 knockdown reduces colony formation.

1 fig 4.PNG (2920 kB)
Fig 4. HSF1 knockdown inhibits wound healing, migration and induction of fibronectin.

1 fig 5.PNG (142 kB)
Fig 5. Fibronectin expression is induced by 3D growth.

1 fig 6.PNG (1736 kB)
Fig 6. TGFβ induction of EMT master-switch transcription factors are reduced upon HSF1 knockdown, and the effect is enhanced upon 3D culturing

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