Cancer cells exploit notch signaling to redefine a supportive cytokine milieu

Michela Colombo, Leonardo Mirandola, Maurizio Chiriva-Internati, Andrea Basile, Massimo Locati, Elena Lesma, Raffaella Chiaramonte, Natalia Platonova

Research output: Contribution to journalReview articlepeer-review


Notch signaling is a well-known key player in the communication between adjacent cells during organ development, when it controls several processes involved in cell differentiation. Notch-mediated communication may occur through the interaction of Notch receptors with ligands on adjacent cells or by a paracrine/endocrine fashion, through soluble molecules that can mediate the communication between cells at distant sites. Dysregulation of Notch pathway causes a number of disorders, including cancer. Notch hyperactivation may be caused by mutations of Notch-related genes, dysregulated upstream pathways, or microenvironment signals. Cancer cells may exploit this aberrant signaling to "educate" the surrounding microenvironment cells toward a pro-tumoral behavior. This may occur because of key cytokines secreted by tumor cells or it may involve the microenvironment through the activation of Notch signaling in stromal cells, an event mediated by a direct cell-to-cell contact and resulting in the increased secretion of several pro-tumorigenic cytokines. Up to now, review articles were mainly focused on Notch contribution in a specific tumor context or immune cell populations. Here, we provide a comprehensive overview on the outcomes of Notch-mediated pathological interactions in different tumor settings and on the molecular and cellular mediators involved in this process. We describe how Notch dysregulation in cancer may alter the cytokine network and its outcomes on tumor progression and antitumor immune response.

Original languageEnglish
Article number1823
JournalFrontiers in Immunology
Issue numberAUG
Publication statusPublished - Aug 14 2018


  • Cancer
  • Chemokine
  • Cytokine
  • Immune response
  • Inflammation
  • Notch
  • Senescence
  • VEGF

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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