Abstract
Initially correlated with hematopoietic precursors, the surface expression of CD133 was also found in epithelial and nonepithelial cells from adult tissues in which it has been associated with a number of biological events. CD133 is expressed in solid tumors as well, including breast cancer, in which most of the studies have been focused on its use as a surface marker for the detection of cells with stem-like properties (i.e., cancer stem cells (CSCs)). Differently with other solid tumors, very limited and in part controversial are the information about the significance of CD133 in breast cancer, the most common malignancy among women in industrialized countries. In this review, we summarize the latest findings about the implication of CD133 in breast tumors, highlighting its role in tumor cells with a triple negative phenotype in which it directly regulates the expression of proteins involved in metastasis and drug resistance. We provide updates about the prognostic role of CD133, underlining its value as an indicator of increased malignancy of both noninvasive and invasive breast tumor cells. The molecular mechanisms at the basis of the regulation of CD133 levels in breast tumors have also been reviewed, highlighting experimental strategies capable to restrain its level that could be taken into account to reduce malignancy and/or to prevent the progression of breast tumors.
Highlights
CD133/prominin 1 (PROM1) is a pentaspan transmembrane single-chain glycoprotein (Figure 1(a)) mainly localized into protrusions of cellular plasma membrane and in the cholesterol-based lipid microdomains, indicative of its involvement in membrane organization [1]
Transcription of human CD133 is driven by five tissuespecific promoters, three of which located in CpG islands and partially regulated by methylation (Figure 1(b)), leading to spliced mRNAs which results in CD133 isoforms with possibly distinct roles [2]
CD133 was firstly revealed as the target of a monoclonal antibody directed against the AC133 epitope expressed by a subpopulation of CD34+ hematopoietic stem cells from the human fetal liver and bone marrow [3]
Summary
CD133/prominin 1 (PROM1) is a pentaspan transmembrane single-chain glycoprotein (Figure 1(a)) mainly localized into protrusions of cellular plasma membrane and in the cholesterol-based lipid microdomains, indicative of its involvement in membrane organization [1]. CD133 is not a stem cell marker and plays a role in morphogenesis, regulating ductal branching and the ratio of luminal to basal cells [10]. E expression of CD133 is deregulated in various solid tumors; despite numerous studies, the role of this surface antigen in tumorigenesis and tumor progression is largely unknown [12]. It is not clear, and in part controversial, the role of CD133 in breast tumors, the most common malignancy and the second cause of cancer-related death among women in industrialized countries. IN Intracellular cysteine-rich domain Region modified by splicing Tyrosine phosphorylation consensus site (a)
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