The IKK/NF-kappaB signaling pathway requires Morgana to drive breast cancer metastasis(227 views) Fusella F, Secli L, Busso E, Krepelova A, Moiso E, Rocca S, Conti L, Annaratone L, Rubinetto C, Mello-grand M, Singh V, Chiorino G, Silengo L, Altruda F, Turco E, Morotti A, Oliviero S, Castellano I, Cavallo F, Provero P, Tarone G, Brancaccio M
Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, 10126, Italy. federica.fusella@unito.it., Department of Life Sciences and Systems Biology, University of Torino, Via Accademia Albertina 13, Torino, 10123, Italy., Human Genetics Foundation (HuGeF), Via Nizza 52, Torino, 10126, Italy., Department of Medical Sciences, University of Torino, Torino, 10126, Italy., Cancer Genomics Laboratory, Fondazione Edo ed Elvo Tempia, Biella, 13900, Italy., Centre for Biological Sciences, Central University of Bihar, Patna Campus, Bihar, 800014, India., Department of Clinical and Biological Sciences, University of Torino, Orbassano, 10043, Italy., Center for Translational Genomics and Bioinformatics, San Raffaele Scientific Institute, Milan, 20132, Italy., Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, 10126, Italy. mara.brancaccio@unito.it.,
References: Not available.
The IKK/NF-kappaB signaling pathway requires Morgana to drive breast cancer metastasis
NF-kappaB 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-kappaB is frequently hyperactivated in several cancers, including triple-negative breast cancer. Here we show that NF-kappaB 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 IkappaBalpha substrate recognition. Morgana silencing blocks metastasis formation in breast cancer mouse models and this phenotype is reverted by IkappaBalpha 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-kappaB target gene expression and poor prognosis in human patients.
The IKK/NF-kappaB signaling pathway requires Morgana to drive breast cancer metastasis