Journal
IMMUNOBIOLOGY
Volume 220, Issue 5, Pages 539-544Publisher
ELSEVIER GMBH, URBAN & FISCHER VERLAG
DOI: 10.1016/j.imbio.2014.12.009
Keywords
HMGB1; Autophagy; RAGE
Categories
Funding
- National Natural Science Foundation of China [81370084, 81101677]
- Postdoctoral Foundation of China [2012M511705, 2013T60508]
- Province in Jiangsu six adults just high peak [2013-WSN-002]
- Postdoctoral Foundation of Jiangsu Province [1102129C]
- Clinical Special Projects of Science and Technology Department of Jiangsu Province [BL2012059]
- Maternal and Child Health Research Projects of Jiangsu Province [F201350]
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Autophagy is a self-digesting mechanism responsible for the removal of long-lived proteins and damaged organelles by lysosomes. It also allows cells to survive during nutrient depletion and/or in the absence of growth factors. High-mobility group protein 1 (HMGB1) is a highly-conserved nuclear protein that has been associated with cell autophagy; however, the mechanisms responsible for this role remain unclear. Many reports have demonstrated that autophagy represents a survival strategy for tumor cells during nutrient depletion, oxidative stress and DNA damage. In the present study, we explored the mechanisms whereby HMGB1 regulates tumor cell autophagy during nutrient depletion (the cells were cultured in Hank's balanced salt solution, HBSS). HMGB1 expression in Lewis cells increased and the protein was shuttled from the nucleus to the cytoplasm and was secreted, coincident with up-regulation of autophagy. Prevention of HMGB1 binding to the receptor for advanced glycation end products (RAGE) or knock-down of HMGB1 expression led to inhibition of autophagy and increased apoptosis. These results demonstrated a positive feedback pathway whereby starvation of Lewis cells promoted HMGB1 secretion, allowing cells to survive by regulating autophagy via a RAGE-HMGB1-extracellular signal-regulated kinase1/2-dependent pathway. These results also implicate HMGB1 as a potential risk factor for cancer growth and metastasis. (C) 2014 Elsevier GmbH. All rights reserved.
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