TY - JOUR
T1 - The IKK/NF-κB signaling pathway requires Morgana to drive breast cancer metastasis
AU - Fusella, F
AU - Seclì, L
AU - Busso, E
AU - Krepelova, A
AU - Moiso, E
AU - Rocca, Stefania
AU - Conti, L
AU - Annaratone, L
AU - Rubinetto, C
AU - Mello-Grand, M
AU - Singh, V
AU - Chiorino, G
AU - Silengo, L
AU - Altruda, F
AU - Turco, Emilia
AU - Morotti, A
AU - Oliviero, Salvatore
AU - Castellano, I
AU - Cavallo, F
AU - Provero, P
AU - Tarone, G
AU - Brancaccio, M
PY - 2017
Y1 - 2017
N2 - 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. © 2017 The Author(s).
AB - 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. © 2017 The Author(s).
U2 - 10.1038/s41467-017-01829-1
DO - 10.1038/s41467-017-01829-1
M3 - Article
VL - 8
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 4
M1 - 1636
ER -