Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Aug 26, 2019; 11(8): 519-534
Published online Aug 26, 2019. doi: 10.4252/wjsc.v11.i8.519
Linking stemness with colorectal cancer initiation, progression, and therapy
Deepak Narayanan Iyer, Wai-Yan Sin, Lui Ng
Deepak Narayanan Iyer, Wai-Yan Sin, Lui Ng, Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
Author contributions: Iyer DN, Sin WY and Ng L equally contributed to the literature review, as well as writing, editing, and revision of the manuscript, and approved the final version of the article to be published.
Conflict-of-interest statement: All the Authors have no conflict of interest related to the manuscript.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Lui Ng, PhD, Research Assistant Professor, Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong, China.
Telephone: +852-3917-9817
Received: February 21, 2019
Peer-review started: February 22, 2019
First decision: June 3, 2019
Revised: June 12, 2019
Accepted: June 20, 2019
Article in press: June 20, 2019
Published online: August 26, 2019

The discovery of cancer stem cells caused a paradigm shift in the concepts of origin and development of colorectal cancer. Several unresolved questions remain in this field though. Are colorectal cancer stem cells the cause or an effect of the disease? How do cancer stem cells assist in colorectal tumor dissemination to distant organs? What are the molecular or environmental factors affecting the roles of these cells in colorectal cancer? Through this review, we investigate the key findings until now and attempt to elucidate the origins, physical properties, microenvironmental niches, as well as the molecular signaling network that support the existence, self-renewal, plasticity, quiescence, and the overall maintenance of cancer stem cells in colorectal cancer. Increasing data show that the cancer stem cells play a crucial role not only in the establishment of the primary colorectal tumor but also in the distant spread of the disease. Hence, we will also look at the mechanisms adopted by cancer stem cells to influence the development of metastasis and evade therapeutic targeting and its role in the overall disease prognosis. Finally, we will illustrate the importance of understanding the biology of these cells to develop improved clinical strategies to tackle colorectal cancer.

Keywords: Cancer stem cell, Colorectal cancer, Tumor microenvironment, Metastasis, Extracellular matrix, Tumor heterogeneity, Resistance, Stemness, Quiescence, Recurrence

Core tip: With the advancement of technology, the importance of deciphering the roles of stem cells in normal and malignant intestinal biology has grown tremendously. Aided by several molecular and environmental factors, evidence suggests that colorectal cancer stem cells exploit the intestinal cellular framework causing the development and spread of the disease, simultaneously promoting a poor prognosis through drug resistance and recurrence-based events. Only by a better understanding of the biology of these cells can there be an improvement in the strategies associated with clinical monitoring and therapeutic targeting required for disease management.