Abstract
The expression of CD44 tags cells with stemness-associated properties (cancer initiating cells or cancer stem cells - CSC). This membrane glycoprotein with a cytoplasmic domain indirectly associated with the cellular cytoskeleton, has a crucial role in tumorigenesis. The CD44 receptor enables the cell to respond to changes in tumor microenvironment, promoting several signaling events related to tumor initiation, progression and fixation in distant host tissues. Although the contribution of this transmembrane protein in gene regulation remains unclear, its overexpression in adenocarcinomas, mostly supported by microRNA (miR)-mediated upregulation of target mRNA, is widely accepted. Herein, we gather the evidence that CD44 is one of the most predominant markers of malignant cells and may be found in diverse phenotypes associated with tumor progression. Additionally, CD44 tumor receptors were found to have different roles at a transcriptional level. Thus, innovative therapeutic strategies should rely heavily on its metastasis-promoting ability. Furthermore, the concept of selectively targeting cell sub-populations may be used to develop specific therapeutic and/or diagnostic systems. An approach based on targeting CD44+ cells might provide a strategy to design guided-therapeutic systems against multiple malignant cells including putative CSC.
Keywords: Cancer stem cells, CD44, epithelial-mesenchymal transition, metastasis, tumor progression.
Current Cancer Drug Targets
Title:Looking out for Cancer Stem Cells’ Properties: The Value-Driving Role of CD44 for Personalized Medicines
Volume: 14 Issue: 9
Author(s): Sara Horta, Ana L. Agostinho, Rita Mateus, Lucilia Pereira, Carolina Pereira, Liliana Capinha, Slavomira Doktorovova, Alexandra Brito and Mafalda Videira
Affiliation:
Keywords: Cancer stem cells, CD44, epithelial-mesenchymal transition, metastasis, tumor progression.
Abstract: The expression of CD44 tags cells with stemness-associated properties (cancer initiating cells or cancer stem cells - CSC). This membrane glycoprotein with a cytoplasmic domain indirectly associated with the cellular cytoskeleton, has a crucial role in tumorigenesis. The CD44 receptor enables the cell to respond to changes in tumor microenvironment, promoting several signaling events related to tumor initiation, progression and fixation in distant host tissues. Although the contribution of this transmembrane protein in gene regulation remains unclear, its overexpression in adenocarcinomas, mostly supported by microRNA (miR)-mediated upregulation of target mRNA, is widely accepted. Herein, we gather the evidence that CD44 is one of the most predominant markers of malignant cells and may be found in diverse phenotypes associated with tumor progression. Additionally, CD44 tumor receptors were found to have different roles at a transcriptional level. Thus, innovative therapeutic strategies should rely heavily on its metastasis-promoting ability. Furthermore, the concept of selectively targeting cell sub-populations may be used to develop specific therapeutic and/or diagnostic systems. An approach based on targeting CD44+ cells might provide a strategy to design guided-therapeutic systems against multiple malignant cells including putative CSC.
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Horta Sara, L. Agostinho Ana, Mateus Rita, Pereira Lucilia, Pereira Carolina, Capinha Liliana, Doktorovova Slavomira, Brito Alexandra and Videira Mafalda, Looking out for Cancer Stem Cells’ Properties: The Value-Driving Role of CD44 for Personalized Medicines, Current Cancer Drug Targets 2014; 14 (9) . https://dx.doi.org/10.2174/1568009614666141111154713
DOI https://dx.doi.org/10.2174/1568009614666141111154713 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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