Effect of naive and cancer-educated fibroblasts on colon cancer cell circadian growth rhythm

Alessia Parascandolo, Raffaella Bonavita, Rosario Astaburuaga, Antonio Sciuto, Stefano Reggio, Enrica Barra, Francesco Corcione, Marco Salvatore, Gianluigi Mazzoccoli, Angela Relógio, Mikko O. Laukkanen

Research output: Contribution to journalArticlepeer-review


Opportunistic modification of the tumour microenvironment by cancer cells enhances tumour expansion and consequently eliminates tumour suppressor components. We studied the effect of fibroblasts on the circadian rhythm of growth and protein expression in colon cancer HCT116 cells and found diminished oscillation in the proliferation of HCT116 cells co-cultured with naive fibroblasts, compared with those co-cultured with tumour-associated fibroblasts (TAFs) or those cultured alone, suggesting that TAFs may have lost or gained factors that regulate circadian phenotypes. Based on the fibroblast paracrine factor analysis, we tested IL6, which diminished HCT116 cell growth oscillation, inhibited early phase cell proliferation, increased early phase expression of the differentiation markers CEA and CDX2, and decreased early phase ERK5 phosphorylation. In conclusion, our data demonstrate how the cancer education of naive fibroblasts influences the circadian parameters of neighbouring cancer cells and highlights a putative role for IL6 as a novel candidate for preoperative treatments.

Original languageEnglish
Article number289
JournalCell Death and Disease
Issue number4
Publication statusPublished - Apr 1 2020

ASJC Scopus subject areas

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research


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