Masquerader: high mobility group box-1 and cancer.
Since its identification a third of a century ago, the high-mobility group box-1 (HMGB1) protein has been linked to varied diverse cellular processes, including release from necrotic cells and secretion by activated macrophages engulfing apoptotic cells. Initially described as solely chromatin-associated, HMGB1 was additionally discovered in the cytoplasm of several types of cultured mammalian cells 6 years later. In addition to its intracellular role, HMGB1 has been identified extracellularly as a putative leaderless cytokine and differentiation factor. In the years since its discovery, HMGB1 has also been implicated in disease states, including Alzheimer's, sepsis, ischemia-reperfusion, arthritis, and cancer. In cancer, overexpression of HMGB1, particularly in conjunction with its receptor for advanced glycation end products, has been associated with the proliferation and metastasis of many tumor types, including breast, colon, melanoma, and others. This review focuses on current knowledge and speculation on the role of HMGB1 in the development of cancer, metastasis, and potential targets for therapy.
Ellerman
Jessica E
JE
Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
Brown
Charles K
CK
de Vera
Michael
M
Zeh
Herbert J
HJ
Billiar
Timothy
T
Rubartelli
Anna
A
Lotze
Michael T
MT
D002465:Cell Movement; D002467:Cell Nucleus / Q000378:metabolism; D024243:HMGB1 Protein / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D011956:Receptors, Cell Surface / Q000378:metabolism; D015398:Signal Transduction
D024243:HMGB1 Protein; D011956:Receptors, Cell Surface