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Open AccessJournal ArticleDOI

HMGB1 in cancer: good, bad, or both?

TLDR
The current knowledge of bothHMGB1′s oncogenic and tumor-suppressive roles and the potential strategies that target HMGB1 for the prevention and treatment of cancer are reviewed.
Abstract
Forty years ago, high mobility group box 1 (HMGB1) was discovered in calf thymus and named according to its electrophoretic mobility in polyacrylamide gels. Now, we know that HMGB1 performs dual functions. Inside the cell, HMGB1 is a highly conserved chromosomal protein acting as a DNA chaperone. Outside of the cell, HMGB1 is a prototypical damage-associated molecular pattern, acting with cytokines, chemokines, and growth factors. During tumor development and in cancer therapy, HMGB1 has been reported to play paradoxical roles in promoting both cell survival and death by regulating multiple signaling pathways, including inflammation, immunity, genome stability, proliferation, metastasis, metabolism, apoptosis, and autophagy. Here, we review the current knowledge of both HMGB1's oncogenic and tumor-suppressive roles and the potential strategies that target HMGB1 for the prevention and treatment of cancer.

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HMGB1 in Health and Disease

TL;DR: High-mobility group box 1 (HMGB1), the most abundant and well-studied HMG protein, senses and coordinates the cellular stress response and plays a critical role not only inside of the cell as a DNA chaperone, chromosome guardian, autophagy sustainer, and protector from apoptotic cell death, but also outside thecell as the prototypic damage associated molecular pattern molecule (DAMP).
Journal ArticleDOI

Interplay between ROS and autophagy in cancer cells, from tumor initiation to cancer therapy

TL;DR: This review will focus on the regulatory role of reactive oxygen species (ROS) and autophagy levels during the course of cancer development, from cellular transformation to the formation of metastasis.
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HMGB1, IL-1α, IL-33 and S100 proteins: dual-function alarmins.

TL;DR: This work has shown that release of alarmins from mesenchymal cells is a highly relevant mechanism by which immune cells can be alerted of tissue damage, and alarmins play a key role in the development of acute or chronic inflammatory diseases and in cancer development.
References
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Journal ArticleDOI

Hallmarks of cancer: the next generation.

TL;DR: Recognition of the widespread applicability of these concepts will increasingly affect the development of new means to treat human cancer.
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A role for mitochondria in NLRP3 inflammasome activation

TL;DR: It is shown that mitophagy/autophagy blockade leads to the accumulation of damaged, ROS-generating mitochondria, and this in turn activates the NLRP3 inflammasome, and may explain the frequent association of mitochondrial damage with inflammatory diseases.
Journal ArticleDOI

Release of chromatin protein HMGB1 by necrotic cells triggers inflammation

TL;DR: It is reported that Hmgb1-/- necrotic cells have a greatly reduced ability to promote inflammation, which proves that the release of HMGB1 can signal the demise of a cell to its neighbours, and cells undergoing apoptosis are programmed to withhold the signal that is broadcast by cells that have been damaged or killed by trauma.
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High-mobility group box 1 protein (HMGB1): nuclear weapon in the immune arsenal.

TL;DR: These features of HMGB1 are discussed and recent advances that have led to the preclinical development of therapeutics that modulateHMGB1 release and activity are summarized.
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