CD44 promotes resistance to apoptosis in human colon cancer cells

Lakshman, Minalini; Subramanian, Vijay; Rubenthiran, Umayal; Jothy, Serge

doi:10.1016/j.yexmp.2004.03.002

Cited by 85 publications

(77 citation statements)

References 28 publications

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“…Antibody-directed activation of variant CD44 in colon carcinoma cell lines has been shown to cause resistance to the drug 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), whereas identical treatment of a carcinoma line expressing the standard, non-variant CD44 isoform had no such effect (Bates et al, 2001). In line with this finding, transfection of colon carcinoma cells containing low levels of CD44 with the v3-10-containing isoform of CD44 conferred resistance to apoptosis induced by etoposide, whereas transfection with standard CD44 had less pronounced effects (Lakshman et al, 2004).…”

Section: Promotion Of Drug Resistance By Hyaluronan Cd44 and Emmprinsupporting

confidence: 62%

Hyaluronan, CD44 and Emmprin: Partners in cancer cell chemoresistance

Toole

Slomiany

2008

Drug Resistance Updates

160

140

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Hyaluronan is not only an important structural component of extracellular matrices but also interacts with cells during dynamic cell processes such as occur in cancer. Consequently, interactions of hyaluronan with tumor cells play important cooperative roles in various aspects of malignancy. Hyaluronan binds to several cell surface receptors, including CD44, thus leading to co-regulation of signaling pathways that are important in regulation of multidrug resistance to anticancer drugs, in particular anti-apoptotic pathways induced by activation of receptor tyrosine kinases. Emmprin, a cell surface glycoprotein of the Ig superfamily, stimulates hyaluronan production and downstream signaling consequences. Emmprin and CD44 also interact with various multidrug transporters of the ABC family and monocarboxylate transporters associated with resistance to cancer therapies. Moreover, hyaluronan-CD44 interactions are critical to these properties in the highly malignant, chemotherapy-resistant cancer stem-like cells. Perturbations of the hyaluronan-CD44 interaction at the plasma membrane by various antagonists result in attenuation of receptor tyrosine kinase and transporter activities and inhibition of tumor progression in vivo. These antagonists, especially small hyaluronan oligomers, may be useful in therapeutic strategies aimed at preventing tumor refractoriness or recurrence due to drug-resistant sub-populations within malignant cancers.

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Section: Promotion Of Drug Resistance By Hyaluronan Cd44 and Emmprinsupporting

confidence: 62%

Hyaluronan, CD44 and Emmprin: Partners in cancer cell chemoresistance

Toole

Slomiany

2008

Drug Resistance Updates

160

140

View full text Add to dashboard Cite

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“…Tight interactions with Fas might reasonably be expected to prevent the interaction with ezrin. This may provide one explanation for the controversial literature surrounding CD44, which has been described as both a pro-apoptotic molecule [40][41][42], and an anti-apoptotic and pro-metastatic protein [43][44][45][46][47]. The present study together with our previous data [26] provide one explanation for this controversy.…”

Section: Cd44 Regulates Apoptosissupporting

confidence: 60%

The CD44 standard/ezrin complex regulates Fas-mediated apoptosis in Jurkat cells

et al. 2007

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The transmembrane receptor CD44 conveys important signals from the extracellular microenvironment to the cytoplasm, a phenomena known as ''outside-in'' signaling. CD44 exists as several isoforms that result from alternative splicing, which differ only in the extracellular domain but yet exhibit different activities. CD44 is a binding partner for the membrane-cytoskeleton cross-linker protein ezrin. In this study, we demonstrate that only CD44 standard (CD44s) colocalizes and interacts with the actin cross-linkers ezrin and moesin using well-characterized cell lines engineered to express different CD44 isoforms. Importantly, we also show that the association CD44s-ezrin-actin is an important modulator of Fas-mediated apoptosis. The results highlight a mechanism by which signals from the extracellular milieu regulate intracellular signaling activities involved in programmed cell death.

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“…For this reason, three activation states of CD44 (inactive, inducible, and active) have been described based on the ability to bind FITC-labeled HA (FITC-HA) (9). The biological function of CD44 has been linked to lymphocyte migration and activation (10 -13), inflammation (14), apoptosis (15,16) and differentiation (17), and CD44 expression is a marker of metastatic potential in certain tumors (18). How these apparently distinct functions arise from a single receptor molecule is complex and may be attributed to multiple mechanistic and structural variations including diversity in ligand binding, signaling pathways, glycosylation patterns, and the expression of variant exons in the extracellular portion of the gene that arise through alternative splicing.…”

Section: N Atural Killer T Cells (Nkt)mentioning

confidence: 99%

“…All cells were washed three times in PBS supplemented with 10% bovine growth serum, fixed in 100 l of 0.05% paraformaldehyde for 10 min at room temperature, and resuspended in HBSS with 5% BSA before analysis by flow cytometry using a FACSCalibur (BD Bioscience) with CellQuest (BD Biosciences) and WinMDI (J. Trotter, University of California, San Diego, CA) software. reverse transcribed with 30 U MultiScribe reverse transcriptase using oligo(dT) 16 primers (1.25 M) in a 40-l reaction volume for 10 min at 25°C and 12 min at 42°C. Second-step PCR was performed using 3 l of the cDNA mixture in 50-l reactions containing 1.5 U AmpliTaq Gold DNA polymerase.…”

Section: Ha Bindingmentioning

confidence: 99%

CD44 Differentially Activates Mouse NK T Cells and Conventional T Cells

Larkin

Renukaradhya

Sriram

et al. 2006

The Journal of Immunology

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NK T (NKT) cells are an important component of the innate immune system and recognize the MHC class I-like CD1d molecule. NKT cells possess significant immunoregulatory activity due to their rapid secretion of large quantities of pro- and anti-inflammatory cytokines following CD1d-dependent stimulation. Because the innate immune system is programmed to respond to a multitude of diverse stimuli and must be able to quickly differentiate between pathogenic and endogenous signals, we hypothesized that, apart from stimulation via the TCR (e.g., CD1d-dependent activation), there must be multiple activation pathways that can be triggered through other cell surface receptors on NKT cells. Therefore, we analyzed the ability of CD44, a structurally diverse cell surface receptor expressed on most cells, to stimulate murine NKT cells, compared with conventional T cells. Stimulation of CD44 through Ab cross-linking or binding to its natural ligands hyaluronan and osteopontin induced NKT cells to secrete cytokines, up-regulate activation markers, undergo morphological changes, and resist activation-induced cell death, whereas conventional T cells only exhibited changes in morphology and protection from activation-induced cell death. This CD44-specific stimulation of NKT cells correlated with their ability to bind hyaluronan. Thus, fundamental differences in CD44 function between these lymphocyte subsets suggest an important biological role for CD44 in the innate immune response.

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CD44 promotes resistance to apoptosis in human colon cancer cells

Cited by 85 publications

References 28 publications

Hyaluronan, CD44 and Emmprin: Partners in cancer cell chemoresistance

Hyaluronan, CD44 and Emmprin: Partners in cancer cell chemoresistance

The CD44 standard/ezrin complex regulates Fas-mediated apoptosis in Jurkat cells

CD44 Differentially Activates Mouse NK T Cells and Conventional T Cells

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