title: Interplay between Inflammation and Stemness in Cancer Cells: The Role of Toll-Like Receptor Signaling.
abstract: Cancer stem cells (CSCs) are a small population of cancer cells that exhibit stemness. These cells contribute to cancer metastasis, treatment resistance, and relapse following therapy; therefore, they may cause malignancy and reduce the success of cancer treatment. Nuclear factor kappa B- (NF-κB-) mediated inflammatory responses increase stemness in cancer cells, and CSCs constitutively exhibit higher NF-κB activation, which in turn increases their stemness. These opposite effects form a positive feedback loop that further amplifies inflammation and stemness in cancer cells, thereby expanding CSC populations in the tumor. Toll-like receptors (TLRs) activate NF-κB-mediated inflammatory responses when stimulated by carcinogenic microbes and endogenous molecules released from cells killed during cancer treatment. NF-κB activation by extrinsic TLR ligands increases stemness in cancer cells. Moreover, it was recently shown that increased NF-κB activity and inflammatory responses in CSCs may be caused by altered TLR signaling during the enrichment of stemness in cancer cells. Thus, the activation of TLR signaling by extrinsic and intrinsic factors drives a positive interplay between inflammation and stemness in cancer cells.
authors.affiliation: Immunology Research Center, National Health Research Institutes, Miaoli 35053, Taiwan.
authors.forename: Da-Wei
authors.initials: DW
authors.lastname: Yeh
authors.affiliation: Institute of Molecular and Genomic Medicine, National Health Research Institutes, Miaoli 35053, Taiwan.
authors.forename: Li-Rung
authors.initials: LR
authors.lastname: Huang
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Miaoli 35053, Taiwan.
authors.forename: Ya-Wen
authors.initials: YW
authors.lastname: Chen
authors.affiliation: Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei 11221, Taiwan.
authors.forename: Chi-Ying F
authors.initials: CF
authors.lastname: Huang
authors.affiliation: Immunology Research Center, National Health Research Institutes, Miaoli 35053, Taiwan; Program in Environmental and Occupational Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
authors.forename: Tsung-Hsien
authors.identifier: 0000-0002-5275-9022
authors.initials: TH
authors.lastname: Chuang
mesh_terms: D006801:Humans; D007249:Inflammation / Q000473:pathology*; D009369:Neoplasms / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000473:pathology*; D015398:Signal Transduction / Q000276:immunology; D051193:Toll-Like Receptors / Q000276:immunology*; D051996:Transcription Factor RelA / Q000378:metabolism*
chemical_list: C498143:RELA protein, human; D051193:Toll-Like Receptors; D051996:Transcription Factor RelA