Linking stemness with colorectal cancer initiation, progression, and therapy

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.