The HMGB1/RAGE inflammatory pathway promotes pancreatic tumor growth by regulating mitochondrial bioenergetics

R. Kang, D. Tang, N. E. Schapiro, T. Loux, K. M. Livesey, T. R. Billiar, H. Wang, B. Van Houten, M. T. Lotze, H. J. Zeh

Research output: Contribution to journalArticle

110 Citations (Scopus)

Abstract

Tumor cells require increased adenosine triphosphate (ATP) to support anabolism and proliferation. The precise mechanisms regulating this process in tumor cells are unknown. Here, we show that the receptor for advanced glycation endproducts (RAGE) and one of its primary ligands, high-mobility group box 1 (HMGB1), are required for optimal mitochondrial function within tumors. We found that RAGE is present in the mitochondria of cultured tumor cells as well as primary tumors. RAGE and HMGB1 coordinately enhanced tumor cell mitochondrial complex I activity, ATP production, tumor cell proliferation and migration. Lack of RAGE or inhibition of HMGB1 release diminished ATP production and slowed tumor growth in vitro and in vivo. These findings link, for the first time, the HMGB1-RAGE pathway with changes in bioenergetics. Moreover, our observations provide a novel mechanism within the tumor microenvironment by which necrosis and inflammation promote tumor progression.

Original languageEnglish (US)
Pages (from-to)567-577
Number of pages11
JournalOncogene
Volume33
Issue number5
DOIs
StatePublished - Jan 30 2014
Externally publishedYes

Fingerprint

Energy Metabolism
Growth
Neoplasms
Adenosine Triphosphate
Cultured Tumor Cells
Tumor Microenvironment
Advanced Glycosylation End Product-Specific Receptor
Cell Movement
Mitochondria
Necrosis
Cell Proliferation
Ligands
Inflammation

Keywords

  • ATP
  • HMGB1
  • inflammation
  • mitochondria
  • pancreatic cancer
  • RAGE

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

The HMGB1/RAGE inflammatory pathway promotes pancreatic tumor growth by regulating mitochondrial bioenergetics. / Kang, R.; Tang, D.; Schapiro, N. E.; Loux, T.; Livesey, K. M.; Billiar, T. R.; Wang, H.; Van Houten, B.; Lotze, M. T.; Zeh, H. J.

In: Oncogene, Vol. 33, No. 5, 30.01.2014, p. 567-577.

Research output: Contribution to journalArticle

Kang, R, Tang, D, Schapiro, NE, Loux, T, Livesey, KM, Billiar, TR, Wang, H, Van Houten, B, Lotze, MT & Zeh, HJ 2014, 'The HMGB1/RAGE inflammatory pathway promotes pancreatic tumor growth by regulating mitochondrial bioenergetics', Oncogene, vol. 33, no. 5, pp. 567-577. https://doi.org/10.1038/onc.2012.631
Kang, R. ; Tang, D. ; Schapiro, N. E. ; Loux, T. ; Livesey, K. M. ; Billiar, T. R. ; Wang, H. ; Van Houten, B. ; Lotze, M. T. ; Zeh, H. J. / The HMGB1/RAGE inflammatory pathway promotes pancreatic tumor growth by regulating mitochondrial bioenergetics. In: Oncogene. 2014 ; Vol. 33, No. 5. pp. 567-577.
@article{fd41efcc17474d0081f52b235139547a,
title = "The HMGB1/RAGE inflammatory pathway promotes pancreatic tumor growth by regulating mitochondrial bioenergetics",
abstract = "Tumor cells require increased adenosine triphosphate (ATP) to support anabolism and proliferation. The precise mechanisms regulating this process in tumor cells are unknown. Here, we show that the receptor for advanced glycation endproducts (RAGE) and one of its primary ligands, high-mobility group box 1 (HMGB1), are required for optimal mitochondrial function within tumors. We found that RAGE is present in the mitochondria of cultured tumor cells as well as primary tumors. RAGE and HMGB1 coordinately enhanced tumor cell mitochondrial complex I activity, ATP production, tumor cell proliferation and migration. Lack of RAGE or inhibition of HMGB1 release diminished ATP production and slowed tumor growth in vitro and in vivo. These findings link, for the first time, the HMGB1-RAGE pathway with changes in bioenergetics. Moreover, our observations provide a novel mechanism within the tumor microenvironment by which necrosis and inflammation promote tumor progression.",
keywords = "ATP, HMGB1, inflammation, mitochondria, pancreatic cancer, RAGE",
author = "R. Kang and D. Tang and Schapiro, {N. E.} and T. Loux and Livesey, {K. M.} and Billiar, {T. R.} and H. Wang and {Van Houten}, B. and Lotze, {M. T.} and Zeh, {H. J.}",
year = "2014",
month = "1",
day = "30",
doi = "10.1038/onc.2012.631",
language = "English (US)",
volume = "33",
pages = "567--577",
journal = "Oncogene",
issn = "0950-9232",
publisher = "Nature Publishing Group",
number = "5",

}

TY - JOUR

T1 - The HMGB1/RAGE inflammatory pathway promotes pancreatic tumor growth by regulating mitochondrial bioenergetics

AU - Kang, R.

AU - Tang, D.

AU - Schapiro, N. E.

AU - Loux, T.

AU - Livesey, K. M.

AU - Billiar, T. R.

AU - Wang, H.

AU - Van Houten, B.

AU - Lotze, M. T.

AU - Zeh, H. J.

PY - 2014/1/30

Y1 - 2014/1/30

N2 - Tumor cells require increased adenosine triphosphate (ATP) to support anabolism and proliferation. The precise mechanisms regulating this process in tumor cells are unknown. Here, we show that the receptor for advanced glycation endproducts (RAGE) and one of its primary ligands, high-mobility group box 1 (HMGB1), are required for optimal mitochondrial function within tumors. We found that RAGE is present in the mitochondria of cultured tumor cells as well as primary tumors. RAGE and HMGB1 coordinately enhanced tumor cell mitochondrial complex I activity, ATP production, tumor cell proliferation and migration. Lack of RAGE or inhibition of HMGB1 release diminished ATP production and slowed tumor growth in vitro and in vivo. These findings link, for the first time, the HMGB1-RAGE pathway with changes in bioenergetics. Moreover, our observations provide a novel mechanism within the tumor microenvironment by which necrosis and inflammation promote tumor progression.

AB - Tumor cells require increased adenosine triphosphate (ATP) to support anabolism and proliferation. The precise mechanisms regulating this process in tumor cells are unknown. Here, we show that the receptor for advanced glycation endproducts (RAGE) and one of its primary ligands, high-mobility group box 1 (HMGB1), are required for optimal mitochondrial function within tumors. We found that RAGE is present in the mitochondria of cultured tumor cells as well as primary tumors. RAGE and HMGB1 coordinately enhanced tumor cell mitochondrial complex I activity, ATP production, tumor cell proliferation and migration. Lack of RAGE or inhibition of HMGB1 release diminished ATP production and slowed tumor growth in vitro and in vivo. These findings link, for the first time, the HMGB1-RAGE pathway with changes in bioenergetics. Moreover, our observations provide a novel mechanism within the tumor microenvironment by which necrosis and inflammation promote tumor progression.

KW - ATP

KW - HMGB1

KW - inflammation

KW - mitochondria

KW - pancreatic cancer

KW - RAGE

UR - http://www.scopus.com/inward/record.url?scp=84893245205&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84893245205&partnerID=8YFLogxK

U2 - 10.1038/onc.2012.631

DO - 10.1038/onc.2012.631

M3 - Article

C2 - 23318458

AN - SCOPUS:84893245205

VL - 33

SP - 567

EP - 577

JO - Oncogene

JF - Oncogene

SN - 0950-9232

IS - 5

ER -