CD44: a stemness driver, regulator, and marker-all in one?

Although the concept of cancer stem cells is still controversial, previous studies have shown that blood cancers, as well as specific types of solid cancers such as colorectal cancer, rely on stem cells during the onset of tumor growth and further tumor development. Moreover, resistance to therapeutic treatment in leukemias such as acute myeloid leukemia and in colorectal cancer can be attributed to a small population of cells with stemness properties known as minimal residual disease. In this review, we look back on the discovery of cancer stem cells and the contribution of the findings in blood cancer to a parallel discovery in solid cancers. We focus on CD44 as a stem cell marker, both in blood cancers and in several types of solid cancers, particularly of the gastrointestinal tract. This review highlights newly discovered molecular mechanisms of action of CD44 which indicate that CD44 has indeed a function in stemness, stem cell maintenance, and drug resistance. We attempt here to make the link between the functions of CD44 isoforms in stemness and their involvement in specific steps of tumor growth and metastasis.