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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-\u03b1, CXCL8\/IL-8, and COX-2 together with PGE2. 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.<\/jats:p>","DOI":"10.3390\/ijms221910701","type":"journal-article","created":{"date-parts":[[2021,10,4]],"date-time":"2021-10-04T09:24:15Z","timestamp":1633339455000},"page":"10701","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":377,"title":["Chronic and Cycling Hypoxia: Drivers of Cancer Chronic Inflammation through HIF-1 and NF-\u03baB Activation: A Review of the Molecular Mechanisms"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1642-1259","authenticated-orcid":false,"given":"Jan","family":"Korbecki","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Medical Chemistry, Pomeranian Medical University in Szczecin, Powsta\u0144c\u00f3w Wielkopolskich 72 Av., 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8517-0364","authenticated-orcid":false,"given":"Donata","family":"Simi\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Medical Chemistry, Pomeranian Medical University in Szczecin, Powsta\u0144c\u00f3w Wielkopolskich 72 Av., 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9777-1378","authenticated-orcid":false,"given":"Magdalena","family":"G\u0105ssowska-Dobrowolska","sequence":"additional","affiliation":[{"name":"Department of Cellular Signalling, Mossakowski Medical Research Institute, Polish Academy of Sciences, Pawi\u0144skiego 5, 02-106 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Listos","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Chod\u017aki 4a St., 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Izabela","family":"Gutowska","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Medical Chemistry, Pomeranian Medical University in Szczecin, Powsta\u0144c\u00f3w Wielkopolskich 72 Av., 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4497-4395","authenticated-orcid":false,"given":"Dariusz","family":"Chlubek","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Medical Chemistry, Pomeranian Medical University in Szczecin, Powsta\u0144c\u00f3w Wielkopolskich 72 Av., 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9187-8895","authenticated-orcid":false,"given":"Irena","family":"Baranowska-Bosiacka","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Medical Chemistry, Pomeranian Medical University in Szczecin, Powsta\u0144c\u00f3w Wielkopolskich 72 Av., 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1670","DOI":"10.3390\/cancers6031670","article-title":"Tumor-associated macrophages as major players in the tumor microenvironment","volume":"6","author":"Chanmee","year":"2014","journal-title":"Cancers"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"7983","DOI":"10.1002\/jcp.27553","article-title":"Contribution of regulatory T cells to cancer: A review","volume":"234","author":"Najafi","year":"2019","journal-title":"J. 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