Concise Review: Emerging Role of CD44 in Cancer Stem Cells: A Promising Biomarker and Therapeutic Target

Yan, Yongmin; Zuo, Xiangsheng; Wei, Daoyan

doi:10.5966/sctm.2015-0048

Cited by 532 publications

(469 citation statements)

References 117 publications

(157 reference statements)

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“…Hyaluronan has key regulatory roles in tissue homeostasis and possesses signaling properties through its interaction with cell surface receptors, such as CD44 and RHAMM (Toole 2004). Most malignant tumors contain elevated amounts of CD44, and many reports showed that CD44 is abundant on the surface of cancer stem cells (Yan et al 2015). The presence of hyaluronan could promote clustering of EGFR and CD44, which form a functional unit on the membrane of tumor cells that could be specifically relevant to lung cancer (Meran et al 2011).…”

Section: Discussionmentioning

confidence: 99%

p38MAPK builds a hyaluronan cancer niche to drive lung tumorigenesis

et al. 2016

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Expansion of neoplastic lesions generates the initial signal that instigates the creation of a tumor niche. Nontransformed cell types within the microenvironment continuously coevolve with tumor cells to promote tumorigenesis. Here, we identify p38MAPK as a key component of human lung cancer, and specifically stromal interactomes, which provides an early, protumorigenic signal in the tissue microenvironment. We found that lung cancer growth depends on short-distance cues produced by the cancer niche in a p38-dependent manner. We identified fibroblast-specific hyaluronan synthesis at the center of p38-driven tumorigenesis, which regulates early stromal fibroblast activation, the conversion to carcinoma-associated fibroblasts (CAFs), and cancer cell proliferation. Systemic down-regulation of p38MAPK signaling in a knock-in model with substitution of activating Tyr182 to phenylalanine or conditional ablation of p38 in fibroblasts has a significant tumor-suppressive effect on K-ras lung tumorigenesis. Furthermore, both Kras-driven mouse lung tumors and orthotopically grown primary human lung cancers show a significant sensitivity to both a chemical p38 inhibitor and an over-the-counter inhibitor of hyaluronan synthesis. We propose that p38MAPK-hyaluronan-dependent reprogramming of the tumor microenvironment plays a critical role in driving lung tumorigenesis, while blocking this process could have far-reaching therapeutic implications.

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Section: Discussionmentioning

confidence: 99%

p38MAPK builds a hyaluronan cancer niche to drive lung tumorigenesis

et al. 2016

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“…88,90 Among the best known examples is CD44, which is expressed in several cell-type specific transcript variants with biomarker potential. 91 A low expression level of isoform CD44v6 has been shown to be associated with improved survival in patients with colorectal cancer 92 and many other types of cancer. CD44 isoform status may also be predictive of response to anti-CD44 treatment in several solid tumor types.…”

Section: Structural Transcript Variationmentioning

confidence: 99%

Aberrant RNA splicing in cancer; expression changes and driver mutations of splicing factor genes

Sveen

Kilpinen²,

Ruusulehto³

et al. 2015

Oncogene

419

412

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Alternative splicing is a widespread process contributing to structural transcript variation and proteome diversity. In cancer, the splicing process is commonly disrupted, resulting in both functional and non-functional end-products. Cancer-specific splicing events are known to contribute to disease progression; however, the dysregulated splicing patterns found on a genome-wide scale have until recently been less well-studied. In this review, we provide an overview of aberrant RNA splicing and its regulation in cancer. We then focus on the executors of the splicing process. Based on a comprehensive catalog of splicing factor encoding genes and analyses of available gene expression and somatic mutation data, we identify cancer-associated patterns of dysregulation. Splicing factor genes are shown to be significantly differentially expressed between cancer and corresponding normal samples, and to have reduced inter-individual expression variation in cancer. Furthermore, we identify enrichment of predicted cancer-critical genes among the splicing factors. In addition to previously described oncogenic splicing factor genes, we propose 24 novel cancer-critical splicing factors predicted from somatic mutations.

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“…76,77 CD44 is a transmembrane glycoprotein that serves as a receptor for various components of extracellular matrix. 78,79 Its most important roles include intermediation in cell-cell and cellmatrix interactions, as well as cancer cell migration.…”

mentioning

confidence: 99%

Quinoline based mono- and bis-(thio)carbohydrazones: synthesis, anticancer activity in 2D and 3D cancer and cancer stem cell models

Božić

Marinković

Bjelogrlić³

et al. 2016

RSC Adv.

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A comparative study of antitumor activity of mono-and bis-quinoline based (thio)carbohydrazones was investigated by a series of tests on two human malignant cell lines: acute monocytic leukemia (THP-1) and pancreatic adenocarcinoma cancer stem cells (AsPC-1). Thiocarbohydrazones (TCHs) revealed superior pro-apoptotic activity over carbohydrazones (CHs) on both tested cell phenotypes, also displaying multi-target profile activities. Programmed cell death triggered by TCHs was partially caspasedependent, mainly caspase-8 related. Activity against cancer stem cells (CSCs) was evaluated on 2D monolayers and 3D spheroidal models, where two out of three tested bis-TCHs successfully stimulated apoptosis accompanied by a reduction in size of treated spheres. Additionally, all bis-TCHs induced significant decrease in percentage of CD44-expressing AsPC-1 cells that indicate on their ability to induce reprogramming of CSC phenotype. Current results highly support further assessment of bisTCHs in order to specify their specific targets in cancer cells and particularly in the CSCs subpopulation.

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Concise Review: Emerging Role of CD44 in Cancer Stem Cells: A Promising Biomarker and Therapeutic Target

Cited by 532 publications

References 117 publications

p38MAPK builds a hyaluronan cancer niche to drive lung tumorigenesis

p38MAPK builds a hyaluronan cancer niche to drive lung tumorigenesis

Aberrant RNA splicing in cancer; expression changes and driver mutations of splicing factor genes

Quinoline based mono- and bis-(thio)carbohydrazones: synthesis, anticancer activity in 2D and 3D cancer and cancer stem cell models

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