Emerging roles of prominin-1 (CD133) in the dynamics of plasma membrane architecture and cell signaling pathways in health and disease

Abstract

Prominin-1 (CD133) is a cholesterol-binding membrane glycoprotein selectively associated with highly curved and prominent membrane structures. It is widely recognized as an antigenic marker of stem cells and cancer stem cells and is frequently used to isolate them from biological and clinical samples. Recent progress in understanding various aspects of CD133 biology in different cell types has revealed the involvement of CD133 in the architecture and dynamics of plasma membrane protrusions, such as microvilli and cilia, including the release of extracellular vesicles, as well as in various signaling pathways, which may be regulated in part by posttranslational modifications of CD133 and its interactions with a variety of proteins and lipids. Hence, CD133 appears to be a master regulator of cell signaling as its engagement in PI3K/Akt, Src-FAK, Wnt/β-catenin, TGF-β/Smad and MAPK/ERK pathways may explain its broad action in many cellular processes, including cell proliferation, differentiation, and migration or intercellular communication. Here, we summarize early studies on CD133, as they are essential to grasp its novel features, and describe recent evidence demonstrating that this unique molecule is involved in membrane dynamics and molecular signaling that affects various facets of tissue homeostasis and cancer development. We hope this review will provide an informative resource for future efforts to elucidate the details of CD133’s molecular function in health and disease.

The Impact of Glycosylation on the Functional Activity of CD133 and the Accuracy of Its Immunodetection

“…CD133 appears to be involved in several signaling pathways, specifically PI3K/Akt [ 73 , 74 ], Src/FAK [ 75 , 76 ], Wnt/β-catenin [ 77 , 78 , 79 ], TGF-β/Smad [ 80 ] and MAPK/ERK [ 81 , 82 , 83 ] (as reviewed in ref. [ 2 ]). This may explain the broad action of CD133 in many cellular processes, including cell proliferation [ 84 , 85 ], apoptosis [ 86 , 87 ] and epithelial–mesenchymal transition [ 88 , 89 ].…”

“…The ongoing interest in the CD133 molecule is due to its strong association with the phenotypes of stem and progenitor cells, including cancer stem cells, which are responsible for tumor relapses and metastasis [ 1 , 2 ]. In this regard, CD133 is often considered as a potential prognostic biomarker for various oncological diseases, as well as a promising target for cancer therapy [ 3 , 4 ].…”