CD44: From adhesion molecules to signalling regulators

Ponta, Helmut; Sherman, Larry S.; Herrlich, Peter

doi:10.1038/nrm1004

Cited by 2,105 publications

(2,117 citation statements)

References 133 publications

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“…This multifunctional capacity is in part due to the expression of different CD44 isoforms resulting from alternative splicing that affect and change the extracellular domain of CD44 (reviewed by Gü nthert 2 ). Further functional variation has been demonstrated in recent reports, namely that CD44 functions as a coreceptor in multiprotein complexes (reviewed by Ponta et al 3 ). The association of CD44 with the integrin VLA-4 abrogates the firm adhesion of cells and increases leukocyte extravasation into sites of inflammation.…”

Section: Introductionmentioning

confidence: 86%

A novel antiapoptotic mechanism based on interference of Fas signaling by CD44 variant isoforms

et al. 2005

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There is growing evidence that one of the central common characteristics of tumor and inflammatory cells is their resistance to programmed cell death. This feature results in the accumulation of harmful cells, which are mostly refractory to Fas (FAS, APO-1)-mediated apoptosis. A molecule found on these cells is the transmembrane receptor CD44 with its variant isoforms (CD44v). The establishment of transfectants expressing different CD44v isoforms allowed us to demonstrate that the CD44v6 and CD44v9 isoforms exhibit an antiapoptotic effect and can block Fas-mediated apoptosis. Moreover, we observed that CD44v6 and CD44v9 colocalize and interact with Fas. Importantly, an anti-CD44v6 antibody can abolish the antiapoptotic effect of CD44v6. These results are the first to show that CD44v isoforms interfere with Fas signaling. Our findings improve the understanding of the pathogenesis of cancer and autoimmunity and open new strategies to treat such disorders.

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Section: Introductionmentioning

confidence: 86%

A novel antiapoptotic mechanism based on interference of Fas signaling by CD44 variant isoforms

et al. 2005

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“…Over-expression of 15-PGDH down-regulates the expression of Bcl-2 protein indicating a role for the 15-PGDH in apoptosis. Cell surface CD44 is the receptor for hyaluronate, a major glycosaminoglycan component of the cellular matrix, and may promote tumor invasion (22). Adhesion to the cellular matrix, a critical step in the metastatic process, has been found to be CD44-dependent in several malignancies (23,24).…”

Section: -Pgdh Is a Tumor Suppressormentioning

confidence: 99%

15-Hydroxyprostaglandin dehydrogenase (15-PGDH) and lung cancer

Tai

Tang

Ding

2007

Prostaglandins & Other Lipid Mediators

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Abstract15-Hydroxyprostaglandin dehydrogenase (15-PGDH) catalyzes NAD + -linked oxidation of 15 (S)-hydroxyl group of prostaglandins and lipoxins and is the key enzyme responsible for the biological inactivation of these eicosanoids. The enzyme was found to be under-expressed as opposed to cyclooxygenase-2 (COX-2) being over-expressed in lung and other tumors. A549 human lung adenocarcinoma cells were used as a model system to study the role of 15-PGDH in lung tumorigenesis. Up-regulation of COX-2 expression by pro-inflammatory cytokines in A549 cells was accompanied by a down-regulation of 15-PGDH expression. Over-expression of COX-2 but not COX-1 by adenoviral-mediated approach also attenuated 15-PGDH expression. Similarly, overexpression of 15-PGDH by the same strategy inhibited IL-1β-induced COX-2 expression. It appears that the expression of COX-2 and 15-PGDH is regulated reciprocally. Adenoviral-mediated transient over-expression of 15-PGDH in A549 cells resulted in apoptosis. Xenograft studies in nude mice also showed tumor suppression with cells transiently over-expressing 15-PGDH. However, cells stably over-expressing 15-PGDH generated tumors faster than those control cells. Examination of different clones of A549 cells stably expressing different levels of 15-PGDH indicated that the levels of 15-PGDH expression correlated positively with those of mesenchymal markers, and negatively with those of epithelial markers. It appears that the stable expression of 15-PGDH induces epithelialmesenchymal transition (EMT) which may account for the tumor promotion in xenograft studies. A number of anti-cancer agents, such as transforming growth factor-β1 (TGF-β1), glucocorticoids and some histone deacetylase inhibitors were found to induce 15-PGDH expression. These results suggest that tumor suppressive action of these agents may, in part, be related to their ability to induce 15-PGDH expression.

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“…CD44 is a cell surface antigen that demonstrates cell adhesion and signaling function (Ponta et al, 2003). CD44 is involved in normal myelopoiesis and lymphopoiesis and is also expressed on leukemia blasts in all acute myeloid leukemia (AML) subtypes (Ghaffari et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

CD44 ligation induces caspase-independent cell death via a novel calpain/AIF pathway in human erythroleukemia cells

et al. 2006

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Ligation of the cell surface molecule CD44 by anti-CD44 monoclonal antibodies (mAbs) has been shown to induce cell differentiation, cell growth inhibition and in some cases, apoptosis in myeloid leukemic cells. We report, herein, that exposure of human erythroleukemic HEL cells to the anti-CD44 mAb A3D8 resulted in cell growth inhibition followed by caspase-independent apoptosis-like cell death. This process was associated with the disruption of mitochondrial membrane potential (DWm), the mitochondrial release of apoptosis-inducing factor (AIF), but not of cytochrome c, and the nuclear translocation of AIF. All these effects including cell death, loss of mitochondrial DWm and AIF release were blocked by pretreatment with the poly (ADP-ribose) polymerase inhibitor isoquinoline. A significant protection against cell death was also observed by using small interfering RNA for AIF. Moreover, we show that calpain protease was activated before the appearance of apoptosis, and that calpain inhibitors or transfection of calpain-siRNA decrease A3D8-induced cell death, and block AIF release. These data suggest that CD44 ligation triggers a novel caspaseindependent cell death pathway via calpain-dependent AIF release in erythroleukemic HEL cells.

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CD44: From adhesion molecules to signalling regulators

Cited by 2,105 publications

References 133 publications

A novel antiapoptotic mechanism based on interference of Fas signaling by CD44 variant isoforms

A novel antiapoptotic mechanism based on interference of Fas signaling by CD44 variant isoforms

15-Hydroxyprostaglandin dehydrogenase (15-PGDH) and lung cancer

CD44 ligation induces caspase-independent cell death via a novel calpain/AIF pathway in human erythroleukemia cells

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