PMID- 27191981
OWN - NLM
STAT- MEDLINE
DCOM- 20180116
LR  - 20220330
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 7
IP  - 25
DP  - 2016 Jun 21
TI  - Crosstalk between the HIF-1 and Toll-like receptor/nuclear factor-kappaB pathways in 
      the oral squamous cell carcinoma microenvironment.
PG  - 37773-37789
LID - 10.18632/oncotarget.9329 [doi]
AB  - Hypoxia is a prominent feature of the microenvironment of solid tumors and may 
      contribute to tumor progression through the oxygen-sensitive transcriptional 
      regulator hypoxia-inducible factor-1 (HIF-1). Chronic inflammation is another 
      typical feature. Inflammatory mediators, including Toll-like receptors (TLRs) and 
      nuclear factor-kappaB (NF-kappaB), play an important role in cancer development. Recent 
      studies have revealed extensive cross-talk between hypoxia and inflammation 
      signaling, though the mechanisms remain unclear. Our results confirm that TLR3 
      and TLR4 are highly expressed in oral squamous cell carcinoma (OSCC). Activation 
      of TLR3 and TLR4 stimulated the expression of HIF-1 through NF-kappaB. In addition, 
      HIF-1 increased the expression of TLR3 and TLR4 through direct promoter binding. 
      Thus, the TLR/NF-kappaB pathway forms a positive feedback loop with HIF-1. These 
      results indicate a novel cross-talk between the TLR/NF-kappaB and HIF-1 signaling, 
      which may contribute to OSCC initiation and progression. With the elucidation of 
      this novel mechanism, it might serve as a basis for future microenvironment 
      targeted cancer therapy.
FAU - Han, Shengwei
AU  - Han S
AD  - Department of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, 
      Medical School of Nanjing University, Nanjing, P.R. China.
AD  - Central Laboratory of Stomatology, Nanjing Stomatological Hospital, Medical 
      School of Nanjing University, Nanjing, P.R. China.
FAU - Xu, Wenguang
AU  - Xu W
AD  - Department of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, 
      Medical School of Nanjing University, Nanjing, P.R. China.
AD  - Central Laboratory of Stomatology, Nanjing Stomatological Hospital, Medical 
      School of Nanjing University, Nanjing, P.R. China.
FAU - Wang, Zhiyong
AU  - Wang Z
AD  - Department of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, 
      Medical School of Nanjing University, Nanjing, P.R. China.
AD  - Central Laboratory of Stomatology, Nanjing Stomatological Hospital, Medical 
      School of Nanjing University, Nanjing, P.R. China.
FAU - Qi, Xiaofeng
AU  - Qi X
AD  - Department of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, 
      Medical School of Nanjing University, Nanjing, P.R. China.
AD  - Central Laboratory of Stomatology, Nanjing Stomatological Hospital, Medical 
      School of Nanjing University, Nanjing, P.R. China.
FAU - Wang, Yufeng
AU  - Wang Y
AD  - Department of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, 
      Medical School of Nanjing University, Nanjing, P.R. China.
AD  - Central Laboratory of Stomatology, Nanjing Stomatological Hospital, Medical 
      School of Nanjing University, Nanjing, P.R. China.
FAU - Ni, Yanhong
AU  - Ni Y
AD  - Central Laboratory of Stomatology, Nanjing Stomatological Hospital, Medical 
      School of Nanjing University, Nanjing, P.R. China.
FAU - Shen, Hao
AU  - Shen H
AD  - Department of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, 
      Medical School of Nanjing University, Nanjing, P.R. China.
AD  - Central Laboratory of Stomatology, Nanjing Stomatological Hospital, Medical 
      School of Nanjing University, Nanjing, P.R. China.
FAU - Hu, Qingang
AU  - Hu Q
AD  - Department of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, 
      Medical School of Nanjing University, Nanjing, P.R. China.
AD  - Central Laboratory of Stomatology, Nanjing Stomatological Hospital, Medical 
      School of Nanjing University, Nanjing, P.R. China.
FAU - Han, Wei
AU  - Han W
AD  - Department of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, 
      Medical School of Nanjing University, Nanjing, P.R. China.
AD  - Central Laboratory of Stomatology, Nanjing Stomatological Hospital, Medical 
      School of Nanjing University, Nanjing, P.R. China.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - 0 (TLR3 protein, human)
RN  - 0 (TLR4 protein, human)
RN  - 0 (Toll-Like Receptor 3)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (VEGFA protein, human)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - O84C90HH2L (Poly I-C)
SB  - IM
MH  - Carcinoma, Squamous Cell/*metabolism
MH  - Cell Hypoxia
MH  - Cell Line, Tumor
MH  - Gene Expression Profiling
MH  - *Gene Expression Regulation, Neoplastic
MH  - HEK293 Cells
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism
MH  - Inflammation
MH  - Lipopolysaccharides/chemistry
MH  - Mouth Neoplasms/*metabolism
MH  - NF-kappa B/*metabolism
MH  - Poly I-C/chemistry
MH  - Signal Transduction
MH  - Toll-Like Receptor 3/metabolism
MH  - Toll-Like Receptor 4/metabolism
MH  - Tumor Microenvironment
MH  - Vascular Endothelial Growth Factor A/metabolism
PMC - PMC5122348
OTO - NOTNLM
OT  - HIF-1
OT  - NF-kappaB
OT  - TLR
OT  - oral squamous cell carcinoma
OT  - tumor microenvironment
COIS- None.
EDAT- 2016/10/23 06:00
MHDA- 2018/01/18 06:00
PMCR- 2016/06/21
CRDT- 2016/05/19 06:00
PHST- 2015/11/19 00:00 [received]
PHST- 2016/04/28 00:00 [accepted]
PHST- 2016/10/23 06:00 [pubmed]
PHST- 2018/01/18 06:00 [medline]
PHST- 2016/05/19 06:00 [entrez]
PHST- 2016/06/21 00:00 [pmc-release]
AID - 9329 [pii]
AID - 10.18632/oncotarget.9329 [doi]
PST - ppublish
SO  - Oncotarget. 2016 Jun 21;7(25):37773-37789. doi: 10.18632/oncotarget.9329.