High Mobility Group Box 1 in Human Cancer

Abstract

<jats:p>High mobility group box 1 (HMGB1) is an extremely versatile protein that is located predominantly in the nucleus of quiescent eukaryotic cells, where it is critically involved in maintaining genomic structure and function. During cellular stress, however, this multifaceted, cytokine-like protein undergoes posttranslational modifications that promote its translocation to the cytosol, from where it is released extracellularly, either actively or passively, according to cell type and stressor. In the extracellular milieu, HMGB1 triggers innate inflammatory responses that may be beneficial or harmful, depending on the magnitude and duration of release of this pro-inflammatory protein at sites of tissue injury. Heightened awareness of the potentially harmful activities of HMGB1, together with a considerable body of innovative, recent research, have revealed that excessive production of HMGB1, resulting from misdirected, chronic inflammatory responses, appears to contribute to all the stages of tumorigenesis. In the setting of established cancers, the production of HMGB1 by tumor cells per se may also exacerbate inflammation-related immunosuppression. These pro-inflammatory mechanisms of HMGB1-orchestrated tumorigenesis, as well as the prognostic potential of detection of elevated expression of this protein in the tumor microenvironment, represent the major thrusts of this review.</jats:p>

Complement C1s and C4d as Prognostic Biomarkers in Renal Cancer: Emergence of Noncanonical Functions of C1s

“…The subcellular localization of C1s in the cytoplasm hints at potential mechanisms by which it can affect fundamental cellular functions. C1s interacts and cleaves HMGB-1 [52], [53], which shuttles between the cytoplasm and the nucleus [54]. In the nucleus, HMGB1 interacts with nucleosomes, transcription factors, and histones, regulating transcription.…”

Inhibition of the Receptor for Advanced Glycation End Products Enhances the Cytotoxic Effect of Gemcitabine in Murine Pancreatic Tumors

“…Importantly, NF-κB is activated following the activation of RAGE by many of its ligands, including HMGB1 [ 17 , 41 , 82 ]. In the classical pathway, NF-κB activation involves the phosphorylation of IκBα by the activated IKKα/IKKβ kinase.…”

Proteins Marking the Sequence of Genotoxic Signaling from Irradiated Mesenchymal Stromal Cells to CD34+ Cells

“…Moreover, diminished eIF3f was detected in CD34+ cells exposed to MSC conditioned medium, which was in line with common suppression in diverse cancers [ 63 , 64 ]. Finally, high mobility group protein B1 (HMGB1) assumes a number of roles in cancer development as well [ 65 ]. HMGB1 enhances DNA repair and chromatin modification after DNA damage [ 66 ].…”