Current Cancer Drug Targets

Ruiwen Zhang 
Texas Tech University Health Sciences Center
1300 Coulter Drive
Amarillo, TX 79106
USA

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Looking out for Cancer Stem Cells’ Properties: The Value-Driving Role of CD44 for Personalized Medicines

Author(s): Sara Horta, Ana L. Agostinho, Rita Mateus, Lucilia Pereira, Carolina Pereira, Liliana Capinha, Slavomira Doktorovova, Alexandra Brito, Mafalda Videira.

Graphical Abstract:


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.

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Article Details

VOLUME: 14
ISSUE: 9
Year: 2014
Page: [832 - 849]
Pages: 18
DOI: 10.2174/1568009614666141111154713
Price: $58