Enhancer reprogramming in tumor progression: a new route towards cancer cell plasticity

Luca Fagnocchi, Vittoria Poli, Alessio Zippo

Research output: Contribution to journalArticlepeer-review


Cancer heterogeneity arises during tumor progression as a consequence of genetic insults, environmental cues, and reversible changes in the epigenetic state, favoring tumor cell plasticity. The role of enhancer reprogramming is emerging as a relevant field in cancer biology as it supports adaptation of cancer cells to those environmental changes encountered during tumor progression and metastasis seeding. In this review, we describe the cancer-related alterations that drive oncogenic enhancer activity, leading to dysregulated transcriptional programs. We discuss the molecular mechanisms of both cis- and trans-factors in overriding the regulatory circuits that maintain cell-type specificity and imposing an alternative, de-regulated enhancer activity in cancer cells. We further comment on the increasing evidence which implicates stress response and aging-signaling pathways in the enhancer landscape reprogramming during tumorigenesis. Finally, we focus on the potential therapeutic implications of these enhancer-mediated subverted transcriptional programs, putting particular emphasis on the lack of information regarding tumor progression and the metastatic outgrowth, which still remain the major cause of mortality related to cancer.

Original languageEnglish
Pages (from-to)1-19
Number of pages19
JournalCellular and Molecular Life Sciences
Publication statusAccepted/In press - Apr 24 2018
Externally publishedYes


  • Cancer
  • Cis-regulatory elements
  • DNA damage
  • Enhancer
  • Epigenetic
  • Metastasis
  • Reprogramming
  • Signaling pathways
  • Transcription factors
  • Tumor progression

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Cellular and Molecular Neuroscience
  • Cell Biology


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