Functional Roles of CD133: More than Stemness Associated Factor Regulated by the Microenvironment

• Published in: Stem cell reviews and reports Vol. 20; no. 1; pp. 25 - 51
• Main Authors: Moreno-Londoño, Angela Patricia, Robles-Flores, Martha
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.01.2024; Springer Nature B.V
• Subjects: 1-Phosphatidylinositol 3-kinase; Adaptability; AKT protein; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Cancer; Cell Biology; Cell differentiation; Cell migration; Cell Self Renewal; Life Sciences; Microenvironments; Neoplastic Stem Cells - metabolism; Phosphatidylinositol 3-Kinases - metabolism; Progenitor cells; Regenerative Medicine/Tissue Engineering; Signal transduction; Signal Transduction - genetics; Stem Cells; Surface markers; Wnt protein; β-Catenin; Cancer stem cell; Stemness associated markers; Tumor microenvironment; CD133
• ISSN: 2629-3269; 2629-3277
• DOI: 10.1007/s12015-023-10647-6

CD133 protein has been one of the most used surface markers to select and identify cancer cells with stem-like features. However, its expression is not restricted to tumoral cells; it is also expressed in differentiated cells and stem/progenitor cells in various normal tissues. CD133 participates in several cellular processes, in part orchestrating signal transduction of essential pathways that frequently are dysregulated in cancer, such as PI3K/Akt signaling and the Wnt/β-catenin pathway. CD133 expression correlates with enhanced cell self-renewal, migration, invasion, and survival under stress conditions in cancer. Aside from the intrinsic cell mechanisms that regulate CD133 expression in each cellular type, extrinsic factors from the surrounding niche can also impact CD33 levels. The enhanced CD133 expression in cells can confer adaptive advantages by amplifying the activation of a specific signaling pathway in a context-dependent manner. In this review, we do not only describe the CD133 physiological functions known so far, but importantly, we analyze how the microenvironment changes impact the regulation of CD133 functions emphasizing its value as a marker of cell adaptability beyond a cancer-stem cell marker. Graphical Abstract