NFE2L3 Controls Colon Cancer Cell Growth through Regulation of DUX4, a CDK1 Inhibitor

Marina Bury, Benjamin Le Calve, Frédéric Lessard, Thomas Dal Maso, James Saliba, Carine Michiels, Gerardo Febeyre, Blank Vloker

Résultats de recherche: Contribution à un journal/une revueArticle

Résumé

Constitutive nuclear factor κB (NF-κB) 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-κB 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-κB 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.

langue originaleAnglais
Pages (de - à)1469-1481.e9
journalCell Reports
Volume29
Numéro de publication6
Les DOIs
étatPublié - 5 nov. 2019

Empreinte digitale

Cyclin-Dependent Kinases
Cell proliferation
Cell growth
Colonic Neoplasms
Tumors
Cells
Cell Cycle
Colon
Growth
Cell Proliferation
Neoplasms
Transcription Factors
Homeobox Genes
Chemical activation
Tissue
Adenocarcinoma
Therapeutics

Citer ceci

Bury, Marina ; Le Calve, Benjamin ; Lessard, Frédéric ; Dal Maso, Thomas ; Saliba, James ; Michiels, Carine ; Febeyre, Gerardo ; Vloker, Blank. / NFE2L3 Controls Colon Cancer Cell Growth through Regulation of DUX4, a CDK1 Inhibitor. Dans: Cell Reports. 2019 ; Vol 29, Numéro 6. p. 1469-1481.e9.
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NFE2L3 Controls Colon Cancer Cell Growth through Regulation of DUX4, a CDK1 Inhibitor. / Bury, Marina; Le Calve, Benjamin; Lessard, Frédéric; Dal Maso, Thomas; Saliba, James; Michiels, Carine; Febeyre, Gerardo; Vloker, Blank.

Dans: Cell Reports, Vol 29, Numéro 6, 05.11.2019, p. 1469-1481.e9.

Résultats de recherche: Contribution à un journal/une revueArticle

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