IKKs and tumor cell plasticity

Abstract

Nuclear factor κB (NF-κB) transcription factors are the central hubs of signaling pathways connecting proinflammatory signals to cell survival, proliferation and cytokine production. In cancers, NF-κB signaling influences many aspects of tumor development, from initiation to metastasis. These functions are mediated by tumor-induced plasticity that allows tumor cells to adapt and survive in changing conditions within the tumor microenvironment. Tumor cell plasticity is shaped by the inflammatory microenvironment in tumors. This review focuses on inhibitor of NF-κB kinases, the direct upstream elements of NF-κB regulation, specifically on their conventional and non-conventional functions in animal models of tumorigenesis from the recent literature.

INH14, a Small‐Molecule Urea Derivative, Inhibits the IKKα/β‐Dependent TLR Inflammatory Response

“…The important role of IKKs in cancer regulation is backed up by multiple studies . IKKs regulate NF‐kB activation, which, in turn, controls crucial steps in tumor development, such as transformation, survival, proliferation, and metastasis.…”

Cancer Stem Cell Biology

“…Tumor microenvironment shapes every facet of the tumor cell plasticity through interactions between tumor cells in different populations and also their interplay with stromal and immune cells. Signaling machinery activated through interactions of these cells with each other and with the surrounding extracellular matrix (ECM) gives rise to spatiotemporal changes in stemness, de-/trans-differentiation and EMT programs to adapt tumor cells to differing conditions within tumor microenvironment (Göktuna et al 2018). Many studies in colorectal cancer provided support for the importance of CSC functions in tumor cell plasticity.…”

“…Hence, tumors do not develop new SC programs altogether. Instead they apply the basic rules operating in tissue SCs to adapt to the ever-changing conditions within the tumor microenvironment (Göktuna et al 2018).…”

“…Tumor progression usually occurs in a multistep manner in which tumor cells progressively acquire mutations leading to novel characteristics so that they can advance from benign to malign during the process. Moreover, not only different tumors from the same patient differ in composition of the cells but also high level of heterogeneity is observed even within the same tumor (Göktuna et al 2018). All these different cells with different evolutionary history may lead to different cell populations harboring distinct mutations and characteristics (Magee et al 2012).…”

The NF‐κB regulator IκBβ exhibits different molecular interactivity and phosphorylation status from IκBα in an IKK2‐catalysed reaction

“…Nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB) is a transcription factor found in nearly all animal cell types and plays a crucial role in various immune responses including cytokine release and microbial infections, while also contributing to cancer initiation and progression . The NF‐κB protein family is composed of five members, p50, p52, p65 (RELA), c‐Rel and RELB, which comprise subunit proteins that form a homodimer or a heterodimer, thereby binding to a target DNA to regulate its expression .…”