title: Mesenchymal stromal cell ciliogenesis is abrogated in response to tumor necrosis factor-α and requires NF-κB signaling.
abstract: The primary cilium is a cell surface-anchored sensory organelle which expression is lost in hypoxic cancer cells and during mesenchymal stromal cells (MSC) adaptation to low oxygen levels. Since pro-inflammatory cues are among the early events which promote tumor angiogenesis, we tested the inflammatory cytokine tumor necrosis factor (TNF)-α and found that it triggered a dose-dependent loss of the primary cilia in MSC. This loss was independent of IFT88 expression, was abrogated by progranulin, an antagonist of the TNF receptor and required the NF-κB signaling intermediates IκB kinase α, β, and γ, as well as NF-κB p65. These findings strengthen the concept that the primary cilium may serve as a biomarker reflecting the tumor-supporting potential of MSC and their capacity to adapt to hypoxic and pro-inflammatory cues.
authors: Laboratoire d'Oncologie Moléculaire, Département de Chimie, Centre de Recherche BioMED, Université du Québec à Montréal, Quebec, Canada.
authors: Amélie
authors: A
authors: Vézina
authors: Laboratoire d'Oncologie Moléculaire, Département de Chimie, Centre de Recherche BioMED, Université du Québec à Montréal, Quebec, Canada.
authors: Eric
authors: E
authors: Vaillancourt-Jean
authors: Laboratoire d'Oncologie Moléculaire, Département de Chimie, Centre de Recherche BioMED, Université du Québec à Montréal, Quebec, Canada.
authors: Stéphanie
authors: S
authors: Albarao
authors: Laboratoire d'Oncologie Moléculaire, Département de Chimie, Centre de Recherche BioMED, Université du Québec à Montréal, Quebec, Canada. Electronic address: annabi.borhane@uqam.ca.
authors: Borhane
authors: B
authors: Annabi
mesh_terms: D000818:Animals; D002923:Cilia / Q000187:drug effects* / Q000378:metabolism*; D005260:Female; D000077155:Granulins; D051550:I-kappa B Kinase / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism*; D000077153:Progranulins; D018124:Receptors, Tumor Necrosis Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000494:pharmacology*
chemical_list: D000077155:Granulins; C120204:Grn protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D016328:NF-kappa B; D000077153:Progranulins; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D051550:I-kappa B Kinase
keywords: Cancer biomarker; Inflammation; Mesenchymal stromal cells; NF-κB; Primary cilium