Cancer Development, Progression, and Therapy: An Epigenetic Overview

Abstract

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.

CCNA1 Promoter Methylation: a Potential Marker for Grading Papanicolaou Smear Cervical Squamous Intraepithelial Lesions

“…Altered DNA methylation of promoter region of certain genes observed in cancer cells and not the normal counterpart, is now known to be causal to disease development and progression (Sarkar et al, 2013). To this end, hypermethylation of promoter-associated CpG islands is now a recognized as a frequent and an early event in many cancers, including cervical neoplasias (Lu et al, 2012).…”

Anti-tumor effects and cellular mechanisms of resveratrol

“…Its ability to suppress cell proliferation, induce apoptosis and suppress metastasis and invasion in a number of cell lines makes resveratrol a natural weapon in the war against cancer (11). Cancer is a multistep disease characterized by uncontrolled cell growth and acquisition of metastatic properties (12). In this process, the activation of oncogenes and/ or the inactivation of tumor suppressor genes lead to cell cycle arrest and apoptotic pathway suppression.…”

Effect of cytostatic proline rich polypeptide-1 on tumor suppressors of inflammation pathway signaling in chondrosarcoma

“…TET1 and TET2 act predominantly as tumor suppressors. Re-introduction and overexpression of these proteins is able to restore the 5hmC content, and to suppress invasion and growth in certain tumors (37)(38)(39)(40)(41). A previous report revealed that a deficiency in SOCS3 may promote tumor development, since it has tumor suppressor functions in numerous cancer cell types (29).…”