期刊
CELLULAR AND MOLECULAR LIFE SCIENCES
卷 75, 期 14, 页码 2537-2555出版社
SPRINGER BASEL AG
DOI: 10.1007/s00018-018-2820-1
关键词
Enhancer; Cis-regulatory elements; Epigenetic; Signaling pathways; Transcription factors; Reprogramming; DNA damage; Cancer; Tumor progression; Metastasis
资金
- Center of Integrative Biology (CIBIO) of the University of Trento
- Fondazione AIRC [AIRC-M ID 21158]
- Italian Ministry of Health [GR-2011-02351172]
- CARIPLO foundation [2014-0915]
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.
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