Mesenchymal stromal cell ciliogenesis is abrogated in response to tumor necrosis factor-α and requires NF-κB signaling

Cancer Lett. 2014 Apr 1;345(1):100-5. doi: 10.1016/j.canlet.2013.11.021. Epub 2013 Dec 11.


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.

Keywords: Cancer biomarker; Inflammation; Mesenchymal stromal cells; NF-κB; Primary cilium.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cilia / drug effects*
  • Cilia / metabolism*
  • Female
  • Granulins
  • I-kappa B Kinase / metabolism
  • Intercellular Signaling Peptides and Proteins / pharmacology
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / drug effects*
  • Mesenchymal Stem Cells / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B / metabolism*
  • Progranulins
  • Receptors, Tumor Necrosis Factor / antagonists & inhibitors
  • Receptors, Tumor Necrosis Factor / metabolism
  • Signal Transduction
  • Tumor Necrosis Factor-alpha / metabolism*
  • Tumor Necrosis Factor-alpha / pharmacology*


  • Granulins
  • Grn protein, mouse
  • Intercellular Signaling Peptides and Proteins
  • NF-kappa B
  • Progranulins
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha
  • I-kappa B Kinase