Cancer Development, Progression, and Therapy: An Epigenetic Overview

International Journal of Molecular Sciences

Sibaji Sarkar¹  Garrick Horn²  Kimberly Moulton²  Anuja Oza²  Shannon Byler²  Shannon Kokolus² 

[1]Cancer Center, L913, Department of Medicine, Boston University School of Medicine, 72 East Concord Street, Boston, MA 02118, USA

关键词: cancer;    epigenetics;    methylation;    demethylation;    hydroxymethylation;    apoptosis;    microRNA;    metastasis;    epithelial-mesenchymal transition (EMT);    therapeutics;   

DOI  :  10.3390/ijms141021087

来源: mdpi

【 摘 要 】

Carcinogenesis involves uncontrolled cell growth, which follows the activation of oncogenes and/or the deactivation of tumor suppression genes. Metastasis requires down-regulation of cell adhesion receptors necessary for tissue-specific, cell–cell attachment, as well as up-regulation of receptors that enhance cell motility. Epigenetic changes, including histone modifications, DNA methylation, and DNA hydroxymethylation, can modify these characteristics. Targets for these epigenetic changes include signaling pathways that regulate apoptosis and autophagy, as well as microRNA. We propose that predisposed normal cells convert to cancer progenitor cells that, after growing, undergo an epithelial-mesenchymal transition. This process, which is partially under epigenetic control, can create a metastatic form of both progenitor and full-fledged cancer cells, after which metastasis to a distant location may occur. Identification of epigenetic regulatory mechanisms has provided potential therapeutic avenues. In particular, epigenetic drugs appear to potentiate the action of traditional therapeutics, often by demethylating and re-expressing tumor suppressor genes to inhibit tumorigenesis. Epigenetic drugs may inhibit both the formation and growth of cancer progenitor cells, thus reducing the recurrence of cancer. Adopting epigenetic alteration as a new hallmark of cancer is a logical and necessary step that will further encourage the development of novel epigenetic biomarkers and therapeutics.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland