Escaping NK cells and recruiting neutrophils: How Morgana/NF-κB signaling promotes metastasis

Abstract

Cancer cells escape immune surveillance and induce immune cell aberrant activation to support tumour growth and progression. We recently reported that Morgana/NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) signaling in breast cancer cells is responsible for NK (Natural Killer) cell inactivation and neutrophil recruitment in the primary tumour and in the lung pre-metastatic niche.

The one thousand and one chaperones of the NF-κB pathway

“…In cancer cells in which the NF-κB pathway is hyperactive, Morgana downregulation hinders NF-κB activation and impairs the production of extracellular mediators required for the formation of a cancer-permissive microenvironment and for the generation of the premetastatic niche in distant organs [96]. Of note, Morgana is overexpressed in a subset of human cancers and, among them, in 36% of human triple negative breast cancers, often characterized by an aberrant activation of NF-B [97,95,98]. Morgana takes part in the mature IKK complex but it is dispensable for the recruitment of HSP90 in the complex or for protecting the IKK complex components from degradation.…”

“…Morgana takes part in the mature IKK complex but it is dispensable for the recruitment of HSP90 in the complex or for protecting the IKK complex components from degradation. Instead, Morgana is essential for the recruitment of IB to the IKK complex and for enabling its phosphorylation [98].…”

Dissecting pharmacological effects of chloroquine in cancer treatment: interference with inflammatory signaling pathways

“…157 However, in triple-negative breast cancer cells, the recognition of substrates by IjBa is dysregulated and therefore IjBa is not sufficient to block expression of NF-jB-driven inflammatory genes. 160 Can there be a prognostic impact of this dichotomy between triple-negative breast cancer and the other breast cancer types with more efficient NF-jB regulation by IjBa? 160 Can there be a prognostic impact of this dichotomy between triple-negative breast cancer and the other breast cancer types with more efficient NF-jB regulation by IjBa?…”

“…158,159 The expressed inflammatory genes inactivate natural killer (NK) cells and recruit neutrophils into both primary tumor and lung pre-metastatic niche, enabling breast cancer cell metastasis. 160 Can there be a prognostic impact of this dichotomy between triple-negative breast cancer and the other breast cancer types with more efficient NF-jB regulation by IjBa?…”