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11:37
In vitro Enrichment of Ovarian Cancer Tumor-initiating Cells
Published on: February 18, 2015
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NFκB Promotes Ovarian Tumorigenesis via Classical Pathways That Support Proliferative Cancer Cells and Alternative
Carrie D House1, Elizabeth Jordan1, Lidia Hernandez1
1Women's Malignancies Branch, National Cancer Institute, Bethesda, Maryland.
Cancer Research
|October 28, 2017
Summary
Nuclear factor-kappa B (NFκB) signaling, particularly the RelB factor, drives ovarian cancer stem cells by regulating aldehyde dehydrogenase (ALDH). This highlights distinct NFκB pathways in cancer recurrence and treatment resistance.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Tumor-initiating cells (TICs) drive advanced-stage recurrent cancers.
- Understanding TICs is crucial for developing effective cancer therapies.
Purpose of the Study:
- To investigate the role of NFκB signaling pathways in supporting ovarian cancer TICs.
- To elucidate the mechanisms by which NFκB regulates cancer stemness-associated genes.
Main Methods:
- Utilized human ovarian cancer xenograft models in mice.
- Assessed the impact of RelB and RelA transcription factors on TIC populations.
- Measured spheroid formation, ALDH expression and activity, chemoresistance, and tumorigenesis.
- Analyzed the regulation of the ALDH1A2 gene.
Main Results:
- Loss of RelB significantly inhibited spheroid formation, ALDH activity, chemoresistance, and tumorigenesis in ovarian cancer models.
- RelB directly regulated aldehyde dehydrogenase (ALDH) expression and activity, crucial for cancer stemness.
- Classical NFκB signaling via RelA was essential for proliferating cells but not for ALDH regulation.
- Distinct NFκB pathways (classical vs. alternative) sustain different cancer cell phenotypes.
Conclusions:
- NFκB signaling, through distinct pathways involving RelB and RelA, plays a critical role in maintaining diverse ovarian cancer phenotypes, including TIC populations.
- Targeting specific NFκB pathways may offer novel therapeutic strategies for recurrent ovarian cancer and overcome chemoresistance.
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