Chapter 23 - Epigentic signaling: regulation of cancer stem cells in colorectal cancer

Abstract

Colorectal cancer (CRC) is one of the most common diseases in people throughout the world, and it's been linked to a series of genetic abnormalities in normal colon epithelial cells. Epigenetic alterations cause the origin and development of metastatic colorectal adenomas. The main basis for the change in emphasis from genetic defects in developing CRC to epigenetic alterations causing CRC is the malignant features and molecular markers that epigenetics encode. Furthermore, accumulating mutations in molecular signaling pathways such as Notch, Wnt, and Hedgehog cause epigenetic alterations in human CRC. Growth of CRC and metastasis are aided by chromatin remodeling and alteration in the two major genes that drive carcinogenesis, tumor suppressor genes and oncogenes. The most prevalent kinds of epigenetic regulation in CRC are DNA methylation, histone modification, and noncoding RNA (ncRNA) expression. ncRNA is another form of epigenetic marker seen in CRC. In most CRC cases involving epigenetic dysregulation, gene methylation is followed by histone modification, which leads to chromatin remodeling and CRC pathogenesis. Cancer stem cell activation is included in a wide range of epigenetic dysregulations. The intricate link and interplay between these dysregulations and genetic aberrations in CRC works as a biomarker for diagnosis, prognosis, and therapeutic response prediction since they emerge early in disease pathogenesis and involve almost all key cancer associated pathways. Better understanding of epigenetic regulation of gene expression in the context of CRC pathogenesis has led to the creation of epigenetic biomarkers for CRC diagnosis and epigenetic medications for CRC therapy. With the purpose of enhancing CRC management, this chapter addresses existing information and new data on the most well studied epigenetic abnormalities in CRC, such as DNA methylation and histone modifications, as well as the role of ncRNAs as epigenetic regulators.