The dual role of C/EBPδ in cancer. (May 2023)

• Record Type: Journal Article
• Authors: Hartl, Leonie; Duitman, JanWillem; Bijlsma, Maarten F.; Spek, C. Arnold
• Is Part Of: Critical reviews in oncology/hematology. Volume 185(2023)
• Publication Date: 2023-05
• Subjects: 5-Aza-dC 5-Aza-2'-deoxycytidine -- 5-FU 5-fluoro-uracil -- ABCA ATP-binding cassette subfamily A -- ABCB ATP-binding cassette subfamily B -- ABCC ATP-binding cassette subfamily C -- AKT AKT serine/threonine kinase 1 -- AP-1 Activator protein 1 -- α-SMA alpha-smooth muscle actin -- ATF4/5 Activating transcription factor 4/5 -- ATG3 Autophagy related 3 -- AURKC Aurora kinase C Bcl-2, B-cell lymphoma 2 -- BET Bromodomain and external-terminal domain -- CD44 CD44 antigen -- CDKN1A Cyclin dependent kinase inhibitor 1 A -- C/EBPα CCAAT/enhancer-binding protein alpha -- C/EBPβ CCAAT/enhancer-binding protein beta -- C/EBPδ CCAAT/enhancer-binding protein delta -- C/EBPε CCAAT/enhancer-binding protein epsilon -- C/EBPγ CCAAT/enhancer-binding protein gamma -- C/EBPζ CCAAT/enhancer-binding protein zeta -- CK2 Casein kinase -- Cop1 E3 ubiquitin-protein ligase COP1 -- COX-2/PTGS2 Carcinoma-associated cyclooxygenase-2 CPO, Coproporphyrinogen oxidase -- CREB2/3 cAMP response element binding protein -- CXCL C-X-C motif chemokine ligand -- CXCR C-X-C motif chemokine receptor -- DNMT DNA cytosine-5-methyltransferase -- DNZNep 3-deazaneplanocin A -- ER Endoplasmic reticulum -- ERα Estrogen receptor alpha -- ETS1 ETS proto-oncogene 1 -- EZH2 Enhancer of zeste homolog 2 -- FBXW7 F-box and WD repeat domain containing 7 -- FOXO1 Forkhead Box O1 -- GLUT1/SLC2A1 Solute carrier family 2 facilitated glucose transporter member 1 -- GSK-3β Glycogen synthase kinase-3 beta -- H3K27 Histone H3 lysine 27 -- HDAC Histone deacetylase -- HuR Human antigen R -- IKK I kappa kinase -- IL Interleukin -- INFγ Interferon gamma -- JAK Janus kinase -- KLHL9 Kelch-like homologue 9 -- CUL3 Cullin-3 -- LC3B-I/II (Microtubule associated protein 1) light chain 3 beta -- Lox1 Lectin-like oxidized low-density lipoprotein (LDL) receptor-1 -- LPS Lipopolysaccharide -- Lys Lysine -- MAFbx Muscle atrophy F-box -- MAPK Mitogen-activated protein kinase -- Mcl-1 Induced myeloid leukemia cell differentiation protein -- MCM4 Minichromosome maintenance complex component 4 -- Miz Msx-interacting-zinc finger -- MMP Matrix metallopeptidase -- mTOR Mammalian target of rapamycin -- MuRF-1 Muscle RING finger 1 -- Myc Myc proto-oncogene protein -- NF-κB Nuclear factor kappa-light-chain-enhancer of activated B cells -- OCT4 Octamer-binding transcription factor 4 -- p300 Histone acetyltransferase p300 -- PcG Polycomb-group proteins -- PDGFA/B Platelet-derived growth factor subunit A/B -- PDGFRα Platelet-derived growth factor receptor alpha -- PERK Protein kinase R-like endoplasmic reticulum kinase -- PPARγ2 Peroxisome proliferator-activated receptor gamma -- PRKDC Protein kinase, DNA-activated catalytic subunit -- PTEN Phosphatase and tensin homolog -- PTX3 Pentraxin 3 -- RB1 Retinoblastoma-associated protein -- RelA/p65 Transcription factor p65 -- ROCK2 Rho-associated coiled-coil forming protein kinase 2 -- S6K1 Ribosomal protein S6 kinase B1 -- SDF4 Stromal cell derived factor 4 -- Ser Serine -- SIAH2 Siah E3 ubiquitin protein ligase 2 -- SMAD3/4 Mothers against decapentaplegic homolog ¾ -- SNAI Snail family transcriptional repressor -- SOX2 SRY-Box transcription factor 2 -- Sp1 Sp1 transcription factor -- Src SRC proto-oncogene, non-receptor tyrosine kinase -- STAT3 Signal transducer and activator of transcription 3 -- SUMO1 Small ubiquitin like modifier 1 -- TCGA The cancer genome atlas -- TGF-β1 Transforming growth factor beta 1 -- Thr Threonine -- TNFα Tumor necrosis factor alpha -- TWIST Twist family BHLH transcription factor -- UBE2V2 Ubiquitin conjugating enzyme E2 V2 -- UTR Untranslated region -- VEGFA Vascular endothelial growth factor alpha -- VEGFR Vascular endothelial growth factor receptor -- pVHL Von Hippel-Lindau -- YY1 YY1 transcription factor -- ZEB1 Zinc finger E-box binding homeobox 1 -- ZNF638 Zinc finger protein 638; CEBPD -- Cancer -- Differentiation -- Hypoxia -- Drug resistance -- Inflammation; Oncology -- Periodicals; Hematology -- Periodicals; 616.994
• DOI: 10.1016/j.critrevonc.2023.103983
• Languages: English
• ISSNs: 1040-8428

Abstract

Abstract: CCAAT/Enhancer-Binding Protein delta (C/EBPδ) is a transcription factor involved in differentiation and inflammation. While sparsely expressed in adult tissues, aberrant expression of C/EBPδ has been associated with different cancers. Initially, re-expression of C/EBPδ in cell cultures limited tumor cell proliferation, assigning it a tumor suppressor role. However, opposing observations were made in pre-clinical models and patients, suggesting that C/EBPδ not only mediates cell proliferation but dictates a broader spectrum of tumorigenesis-related effects. It is now widely accepted that C/EBPδ contributes to an inflammatory, tumor-promoting microenvironment, aids hypoxia adaption and contributes to the recruitment of blood vessels for improved nutrient supply to tumor cells and facilitated extravasation. This review summarizes the work published on this transcription factor in the field of cancer over the past decade. It points out areas in which a consensus on C/EBPδ's role appears to emerge and seek to explain seemingly contradictory results. Highlights: C/EBPδ can induce tumor-limiting differentiation and halt cell cycle progression. But C/EBPδ also forms a positive feedback-loop with HIF-1α to aid hypoxia adaption. C/EBPδ promotes drug resistance in tumor and stromal cells via diverse mechanisms. The stromal compartment is further remodeled by C/EBPδ to facilitate tumorigenesis. C/EBPδ's anti-tumor effects are often overruled by its tumor-promoting activities.