The IKK/NF-κB signaling pathway requires Morgana to drive breast cancer metastasis

Federica Fusella (), Laura Seclì, Elena Busso, Anna Krepelova, Enrico Moiso, Stefania Rocca, Laura Conti, Laura Annaratone, Cristina Rubinetto, Maurizia Mello-Grand, Vijay Singh, Giovanna Chiorino, Lorenzo Silengo, Fiorella Altruda, Emilia Turco, Alessandro Morotti, Salvatore Oliviero, Isabella Castellano, Federica Cavallo, Paolo Provero, Guido Tarone and Mara Brancaccio ()
Additional contact information
Federica Fusella: University of Torino
Laura Seclì: University of Torino
Elena Busso: University of Torino
Anna Krepelova: University of Torino
Enrico Moiso: University of Torino
Stefania Rocca: University of Torino
Laura Conti: University of Torino
Laura Annaratone: University of Torino
Cristina Rubinetto: University of Torino
Maurizia Mello-Grand: Fondazione Edo ed Elvo Tempia
Vijay Singh: Fondazione Edo ed Elvo Tempia
Giovanna Chiorino: Fondazione Edo ed Elvo Tempia
Lorenzo Silengo: University of Torino
Fiorella Altruda: University of Torino
Emilia Turco: University of Torino
Alessandro Morotti: University of Torino
Salvatore Oliviero: University of Torino
Isabella Castellano: University of Torino
Federica Cavallo: University of Torino
Paolo Provero: University of Torino
Guido Tarone: University of Torino
Mara Brancaccio: University of Torino

Nature Communications, 2017, vol. 8, issue 1, 1-17

Abstract: Abstract NF-κB is a transcription factor involved in the regulation of multiple physiological and pathological cellular processes, including inflammation, cell survival, proliferation, and cancer cell metastasis. NF-κB is frequently hyperactivated in several cancers, including triple-negative breast cancer. Here we show that NF-κB activation in breast cancer cells depends on the presence of the CHORDC1 gene product Morgana, a previously unknown component of the IKK complex and essential for IκBα substrate recognition. Morgana silencing blocks metastasis formation in breast cancer mouse models and this phenotype is reverted by IκBα downregulation. High Morgana expression levels in cancer cells decrease recruitment of natural killer cells in the first phases of tumor growth and induce the expression of cytokines able to attract neutrophils in the primary tumor, as well as in the pre-metastatic lungs, fueling cancer metastasis. In accordance, high Morgana levels positively correlate with NF-κB target gene expression and poor prognosis in human patients.

Date: 2017
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01829-1

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DOI: 10.1038/s41467-017-01829-1

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