PMID- 34639040
OWN - NLM
STAT- MEDLINE
DCOM- 20211028
LR  - 20211028
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 22
IP  - 19
DP  - 2021 Oct 2
TI  - Chronic and Cycling Hypoxia: Drivers of Cancer Chronic Inflammation through HIF-1 
      and NF-kappaB Activation: A Review of the Molecular Mechanisms.
LID - 10.3390/ijms221910701 [doi]
LID - 10701
AB  - Chronic (continuous, non-interrupted) hypoxia and cycling (intermittent, 
      transient) hypoxia are two types of hypoxia occurring in malignant tumors. They 
      are both associated with the activation of hypoxia-inducible factor-1 (HIF-1) and 
      nuclear factor kappaB (NF-kappaB), which induce changes in gene expression. This paper 
      discusses in detail the mechanisms of activation of these two transcription 
      factors in chronic and cycling hypoxia and the crosstalk between both signaling 
      pathways. In particular, it focuses on the importance of reactive oxygen species 
      (ROS), reactive nitrogen species (RNS) together with nitric oxide synthase, 
      acetylation of HIF-1, and the action of MAPK cascades. The paper also discusses 
      the importance of hypoxia in the formation of chronic low-grade inflammation in 
      cancerous tumors. Finally, we discuss the effects of cycling hypoxia on the tumor 
      microenvironment, in particular on the expression of VEGF-A, CCL2/MCP-1, 
      CXCL1/GRO-alpha, CXCL8/IL-8, and COX-2 together with PGE(2). These factors induce 
      angiogenesis and recruit various cells into the tumor niche, including 
      neutrophils and monocytes which, in the tumor, are transformed into 
      tumor-associated neutrophils (TAN) and tumor-associated macrophages (TAM) that 
      participate in tumorigenesis.
FAU - Korbecki, Jan
AU  - Korbecki J
AUID- ORCID: 0000-0003-1642-1259
AD  - Department of Biochemistry and Medical Chemistry, Pomeranian Medical University 
      in Szczecin, Powstancow Wielkopolskich 72 Av., 70-111 Szczecin, Poland.
FAU - Siminska, Donata
AU  - Siminska D
AUID- ORCID: 0000-0001-8517-0364
AD  - Department of Biochemistry and Medical Chemistry, Pomeranian Medical University 
      in Szczecin, Powstancow Wielkopolskich 72 Av., 70-111 Szczecin, Poland.
FAU - Gassowska-Dobrowolska, Magdalena
AU  - Gassowska-Dobrowolska M
AUID- ORCID: 0000-0001-9777-1378
AD  - Department of Cellular Signalling, Mossakowski Medical Research Institute, Polish 
      Academy of Sciences, Pawinskiego 5, 02-106 Warsaw, Poland.
FAU - Listos, Joanna
AU  - Listos J
AD  - Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, 
      Chodzki 4a St., 20-093 Lublin, Poland.
FAU - Gutowska, Izabela
AU  - Gutowska I
AD  - Department of Biochemistry and Medical Chemistry, Pomeranian Medical University 
      in Szczecin, Powstancow Wielkopolskich 72 Av., 70-111 Szczecin, Poland.
FAU - Chlubek, Dariusz
AU  - Chlubek D
AUID- ORCID: 0000-0003-4497-4395
AD  - Department of Biochemistry and Medical Chemistry, Pomeranian Medical University 
      in Szczecin, Powstancow Wielkopolskich 72 Av., 70-111 Szczecin, Poland.
FAU - Baranowska-Bosiacka, Irena
AU  - Baranowska-Bosiacka I
AUID- ORCID: 0000-0001-9187-8895
AD  - Department of Biochemistry and Medical Chemistry, Pomeranian Medical University 
      in Szczecin, Powstancow Wielkopolskich 72 Av., 70-111 Szczecin, Poland.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20211002
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Biomarkers)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Inflammation Mediators)
RN  - 0 (NF-kappa B)
RN  - 0 (Reactive Oxygen Species)
RN  - 31C4KY9ESH (Nitric Oxide)
SB  - IM
MH  - Biomarkers
MH  - Disease Susceptibility
MH  - Enzyme Activation
MH  - Humans
MH  - Hypoxia/genetics/*metabolism
MH  - Hypoxia-Inducible Factor 1/genetics/*metabolism
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
MH  - Inflammation/etiology/*metabolism/pathology
MH  - Inflammation Mediators/metabolism
MH  - Models, Biological
MH  - Molecular Targeted Therapy
MH  - NF-kappa B/*metabolism
MH  - Neoplasms/drug therapy/etiology/*metabolism/pathology
MH  - Nitric Oxide/metabolism
MH  - Oxidation-Reduction
MH  - Reactive Oxygen Species/metabolism
MH  - Tumor Microenvironment
PMC - PMC8509318
OTO - NOTNLM
OT  - HIF-1alpha
OT  - HIF-1beta
OT  - NF-kappaB
OT  - cancer
OT  - cycling hypoxia
OT  - hypoxia-inducible factor
OT  - low-grade inflammation
OT  - tumor
COIS- The authors declare no conflict of interest.
EDAT- 2021/10/14 06:00
MHDA- 2021/10/29 06:00
PMCR- 2021/10/02
CRDT- 2021/10/13 01:04
PHST- 2021/09/15 00:00 [received]
PHST- 2021/09/28 00:00 [revised]
PHST- 2021/10/01 00:00 [accepted]
PHST- 2021/10/13 01:04 [entrez]
PHST- 2021/10/14 06:00 [pubmed]
PHST- 2021/10/29 06:00 [medline]
PHST- 2021/10/02 00:00 [pmc-release]
AID - ijms221910701 [pii]
AID - ijms-22-10701 [pii]
AID - 10.3390/ijms221910701 [doi]
PST - epublish
SO  - Int J Mol Sci. 2021 Oct 2;22(19):10701. doi: 10.3390/ijms221910701.