Non-coding RNAs Functioning in Colorectal Cancer Stem Cells
In recent years, the hypothesis of the presence of tumor-initiating cancer stem cells (CSCs) has received a considerable support. This model suggested the existence of CSCs which, thanks to their self-renewal properties, are able to drive the expansion an
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Non-coding RNAs Functioning in Colorectal Cancer Stem Cells Daniele Fanale, Nadia Barraco, Angela Listì, Viviana Bazan, and Antonio Russo
Abstract
In recent years, the hypothesis of the presence of tumor-initiating cancer stem cells (CSCs) has received a considerable support. This model suggested the existence of CSCs which, thanks to their self-renewal properties, are able to drive the expansion and the maintenance of malignant cell populations with invasive and metastatic potential in cancer. Increasing evidence showed the ability of such cells to acquire self-renewal, multipotency, angiogenic potential, immune evasion, symmetrical and asymmetrical divisions which, along with the presence of several DNA repair mechanisms, further enhance their oncogenic potential making them highly resistant to common anticancer treatments. The main signaling pathways involved in the homeostasis of colorectal (CRC) stem cells are the Wnt, Notch, Sonic Hedgehog, and Bone Morfogenic Protein (BMP) pathways, which are mostly responsible for all the features that have been widely referred to stem cells. The same pathways have been identified in colorectal cancer stem cells (CRCSCs), conferring a more aggressive phenotype compared to non-stem CRC cells. Recently, several evidences suggested that non-coding RNAs (ncRNAs) may play a crucial role in the regulation of different biological mechanisms in CRC, by modulating the expression of critical stem cell transcription factors that have been found active in CSCs. In this chapter, we will discuss the involvement of ncRNAs, especially microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), in stemness acquisition and maintenance by CRCSCs, through the regulation
D. Fanale • N. Barraco • A. Listì • V. Bazan A. Russo (*) Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Via del Vespro 129, 90127 Palermo, Italy e-mail: [email protected]; [email protected]; [email protected]; [email protected]; [email protected] © Springer International Publishing Switzerland 2016 O. Slaby, G.A. Calin (eds.), Non-coding RNAs in Colorectal Cancer, Advances in Experimental Medicine and Biology 937, DOI 10.1007/978-3-319-42059-2_5
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of pathways modulating the CSC phenotype and growth, carcinogenesis, differentiation, and epithelial to mesenchymal transition (EMT). Keywords
Cancer stem cells • Colorectal cancer • Differentiation • Epithelialmesenchymal transition • MicroRNAs • Non-coding RNAs • Self-renewal • Signaling pathways • Stemness • Tumorigenicity
5.1
Introduction
Colorectal cancer (CRC) is one of the most common malignant tumors worldwide representing the second leading cause of cancerrelated death in the Western Europe countries and the third in the United States [1, 2]. Although, in the last few years, early detection methods and new therapeutic strategies have been implemented in order to prolong survival and improve life quality of patients, however, the development resistance mechanisms to chemo- and rad
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