PMID- 29696133
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240323
IS  - 2234-943X (Print)
IS  - 2234-943X (Electronic)
IS  - 2234-943X (Linking)
VI  - 8
DP  - 2018
TI  - Classical NF-kappaB Metabolically Reprograms Sarcoma Cells Through Regulation of 
      Hexokinase 2.
PG  - 104
LID - 10.3389/fonc.2018.00104 [doi]
LID - 104
AB  - BACKGROUND: Metabolic reprogramming has emerged as a cancer hallmark, and one of 
      the well-known cancer-associated metabolic alterations is the increase in the 
      rate of glycolysis. Recent reports have shown that both the classical and 
      alternative signaling pathways of nuclear factor kappaB (NF-kappaB) play important roles 
      in controlling the metabolic profiles of normal cells and cancer cells. However, 
      how these signaling pathways affect the metabolism of sarcomas, specifically 
      rhabdomyosarcoma (RMS) and osteosarcoma (OS), has not been characterized. 
      METHODS: Classical NF-kappaB activity was inhibited through overexpression of the 
      IkappaBalpha super repressor of NF-kappaB in RMS and OS cells. Global gene expression 
      analysis was performed using Affymetrix GeneChip Human Transcriptome Array 2.0, 
      and data were interpreted using gene set enrichment analysis. Seahorse Bioscience 
      XF(e)24 was used to analyze oxygen consumption rate as a measure of aerobic 
      respiration. RESULTS: Inhibition of classical NF-kappaB activity in sarcoma cell 
      lines restored alternative signaling as well as an increased oxidative 
      respiratory metabolic phenotype in vitro. In addition, microarray analysis 
      indicated that inhibition of NF-kappaB in sarcoma cells reduced glycolysis. We showed 
      that a glycolytic gene, hexokinase (HK) 2, is a direct NF-kappaB transcriptional 
      target. Knockdown of HK2 shifted the metabolic profile in sarcoma cells away from 
      aerobic glycolysis, and re-expression of HK2 rescued the metabolic shift induced 
      by inhibition of NF-kappaB activity in OS cells. CONCLUSION: These findings suggest 
      that classical signaling of NF-kappaB plays a crucial role in the metabolic profile 
      of pediatric sarcomas potentially through the regulation of HK2.
FAU - Londhe, Priya
AU  - Londhe P
AD  - Department of Cancer Biology and Genetics, The Ohio State University, Columbus, 
      OH, United States.
AD  - Arthur G. James Comprehensive Cancer Center, The Ohio State University, Columbus, 
      OH, United States.
FAU - Yu, Peter Y
AU  - Yu PY
AD  - Arthur G. James Comprehensive Cancer Center, The Ohio State University, Columbus, 
      OH, United States.
AD  - Medical Student Research Program, The Ohio State University, Columbus, OH, United 
      States.
FAU - Ijiri, Yuichi
AU  - Ijiri Y
AD  - Department of Cancer Biology and Genetics, The Ohio State University, Columbus, 
      OH, United States.
AD  - Arthur G. James Comprehensive Cancer Center, The Ohio State University, Columbus, 
      OH, United States.
FAU - Ladner, Katherine J
AU  - Ladner KJ
AD  - Department of Cancer Biology and Genetics, The Ohio State University, Columbus, 
      OH, United States.
AD  - Arthur G. James Comprehensive Cancer Center, The Ohio State University, Columbus, 
      OH, United States.
FAU - Fenger, Joelle M
AU  - Fenger JM
AD  - Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio 
      State University, Columbus, OH, United States.
FAU - London, Cheryl
AU  - London C
AD  - Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio 
      State University, Columbus, OH, United States.
AD  - Cummings School of Veterinary Medicine, Tufts University, Grafton, MA, United 
      States.
FAU - Houghton, Peter J
AU  - Houghton PJ
AD  - Greehey Children's Research Institute, University of Texas Health Science Center, 
      San Antonio, TX, United States.
FAU - Guttridge, Denis C
AU  - Guttridge DC
AD  - Department of Cancer Biology and Genetics, The Ohio State University, Columbus, 
      OH, United States.
AD  - Arthur G. James Comprehensive Cancer Center, The Ohio State University, Columbus, 
      OH, United States.
LA  - eng
GR  - K01 OD019923/OD/NIH HHS/United States
GR  - P30 CA016058/CA/NCI NIH HHS/United States
GR  - R01 CA143082/CA/NCI NIH HHS/United States
GR  - UL1 TR001070/TR/NCATS NIH HHS/United States
PT  - Journal Article
DEP - 20180411
PL  - Switzerland
TA  - Front Oncol
JT  - Frontiers in oncology
JID - 101568867
PMC - PMC5904193
OTO - NOTNLM
OT  - hexokinase
OT  - metabolism
OT  - nuclear factor kappa B
OT  - osteosarcoma
OT  - rhabdomyosarcoma
OT  - sarcoma
EDAT- 2018/04/27 06:00
MHDA- 2018/04/27 06:01
PMCR- 2018/01/01
CRDT- 2018/04/27 06:00
PHST- 2017/05/18 00:00 [received]
PHST- 2018/03/23 00:00 [accepted]
PHST- 2018/04/27 06:00 [entrez]
PHST- 2018/04/27 06:00 [pubmed]
PHST- 2018/04/27 06:01 [medline]
PHST- 2018/01/01 00:00 [pmc-release]
AID - 10.3389/fonc.2018.00104 [doi]
PST - epublish
SO  - Front Oncol. 2018 Apr 11;8:104. doi: 10.3389/fonc.2018.00104. eCollection 2018.