Journal
CELL REPORTS
Volume 29, Issue 6, Pages 1469-+Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2019.09.087
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Funding
- Canadian Government through Genome Canada
- McGill Integrated Cancer Research Training Program (MICRTP, Canada)
- Le Fonds de recherche du Quebec -Sante (FRQS, Canada)
- Cole Foundation (Canada)
- Televie fellowship (FNRS, Belgium)
- FRQS
- CRS (Cancer Research Society, Canada)
- Fund for Research training in Industry and Agriculture (FRIA, Belgium)
- SEG (Lebanon) studentship
- MICRTP studentship
- Canadian Institutes of Health Research (CIHR, Canada) [MOP-97932, PJT-152937]
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Constitutive nuclear factor kappa B (NF-kappa B) activation is a hallmark of colon tumor growth. Cyclin-dependent kinases (CDKs) are critical cell-cycle regulators, and inhibition of CDK activity has been used successfully as anticancer therapy. Here, we show that the NFE2L3 transcription factor functions as a key regulator in a pathway that links NF-kappa B signaling to the control of CDK1 activity, thereby driving colon cancer cell proliferation. We found that NFE2L3 expression is regulated by the RELA subunit of NF-kappa B and that NFE2L3 levels are elevated in patients with colon adenocarcinoma when compared with normal adjacent tissue. Silencing of NFE2L3 significantly decreases colon cancer cell proliferation in vitro and tumor growth in vivo. NFE2L3 knockdown results in increased levels of double homeobox factor 4 (DUX4), which functions as a direct inhibitor of CDK1. The discovered oncogenic pathway governing cell-cycle progression may open up unique avenues for precision cancer therapy.
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