Death Receptor-3, a New E-Selectin Counter-Receptor that Confers Migration and Survival Advantages to Colon Carcinoma Cells by Triggering p38 and ERK MAPK Activation

Gout, Stéphanie; Morin, Chantale; Houle, François; Huot, Jacques

doi:10.1158/0008-5472.can-05-4605

Cited by 93 publications

(98 citation statements)

References 46 publications

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“…Rat Neu2 also decreased sialyl-Le x in mouse colon 26 cells (28), whereas human NEU2 is almost absent in colon mucosa. DR3 glycoproteins of the death receptor family may include sialyl-Le a and sialyl-Le x , and could bind to E-selectin in HT29 and Lovo cells (39), impacting on cell motility and cell survival. As our previous study (19) showed that NEU4S enhanced TRAIL-induced apoptosis in colon cancer cells, it is conceivable that it desialylates the sialyl Lewis antigens on DR3 glycoproteins, thus reducing their binding to E-selectin and inhibiting cell motility and survival.…”

Section: Discussionmentioning

confidence: 99%

“…Pathway-Previous observations have showed that sialyl-Le a and sialyl-Le x regulate cell motility (39). To test whether NEU4 affects cell migration through desialyla- Homogenates from HEK293T cells transfected with the respective sialidase cDNAs were used as enzyme sources, and essentially equal amounts for each sialidase were applied.…”

Section: Neu4s Suppresses E-selectin-induced Cell Motility Through Acmentioning

confidence: 99%

“…To clarify details with reference to signal transduction, we focused attention on the p38/Hsp27 pathway. It is known that binding of sialyl-Le a and sialyl-Le x to E-selectin activates p38 signaling in cancer cells (12,39), resulting in stimulation of phosphorylation of various transcription factors and MAPKAP kinase 2, with subsequent activation of MAPKAP kinase 2 and Hsp27, the actin polymerizing factor (40). To investigate the influence of NEU4S on cell motility, HT29 cells were stimulated with E-selectin and the phosphorylation levels were assessed.…”

Section: Neu4s Suppresses E-selectin-induced Cell Motility Through Acmentioning

confidence: 99%

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Regulation of Sialyl Lewis Antigen Expression in Colon Cancer Cells by Sialidase NEU4

Shiozaki

Yamaguchi

Takahashi

et al. 2011

Journal of Biological Chemistry

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Sialyl Lewis antigens, sialyl Lewis a and sialyl Lewis x, are utilized as tumor markers, and their increase in cancer is associated with tumor progression by enhancement of cancer cell adhesion to endothelial E-selectin. However, regulation mechanisms are not fully understood. We previously demonstrated that NEU4 is the only sialidase efficiently acting on mucins and it is downregulated in colon cancer. To elucidate the significance of NEU4 down-regulation, we investigated sialyl Lewis antigens as endogenous substrates for the sialidase. NEU4 was found to hydrolyze the antigens in vitro and decrease cell surface levels much more effectively than other sialidases. Western blot, thin layer chromatography, and metabolic inhibition studies of desialylation products revealed NEU4 to preferentially catalyze sialyl Lewis antigens expressed on O-glycans. Cell adhesion to and motility and growth on E-selectin were significantly reduced by NEU4. E-selectin stimulation of colon cancer cells enhanced cell motility through activation of the p38/Hsp27/actin reorganization pathway, whereas NEU4 attenuated the signaling. On immunocytochemical analysis, some NEU4 molecules were localized at cell surfaces. Under hypoxia conditions whereby the antigens were increased concomitantly with several sialyl-and fucosyltransferases, NEU4 expression was markedly decreased. These results suggest that NEU4 plays an important role in control of sialyl Lewis antigen expression and its impairment in colon cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Neu4s Suppresses E-selectin-induced Cell Motility Through Acmentioning

confidence: 99%

Section: Neu4s Suppresses E-selectin-induced Cell Motility Through Acmentioning

confidence: 99%

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Regulation of Sialyl Lewis Antigen Expression in Colon Cancer Cells by Sialidase NEU4

Shiozaki

Yamaguchi

Takahashi

et al. 2011

Journal of Biological Chemistry

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“…14 In cancer cells, p38a/b are required for breast and colorectal cancer cell migration and metastasis formation in mice. 15,16 However, over-activation of p38 by a constitutively active form of its upstream kinase (MKK6EE) eliminates the tumor-prone phenotype of mice obtained by intercrossing transgenic mice with breast-restricted expression of Wip1, the p53-induced phosphatase targeting p38 and the oncogene ErbB2. 17 Moreover, p38a/b contribute to TGFb-dependent tumor progression by inducing epithelial to mesenchymal transdifferentiation and cell migration, 18 and to rat chondrosarcoma cell proliferation.…”

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confidence: 99%

A novel cell type-specific role of p38α in the control of autophagy and cell death in colorectal cancer cells

et al. 2006

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Cancer develops when molecular pathways that control the fine balance between proliferation, differentiation, autophagy and cell death undergo genetic deregulation. The prospects for further substantial advances in the management of colorectal cancer reside in a systematic genetic and functional dissection of these pathways in tumor cells. In an effort to evaluate the impact of p38 signaling on colorectal cancer cell fate, we treated HT29, Caco2, Hct116, LS174T and SW480 cell lines with the inhibitor SB202190 specific for p38a/b kinases. We report that p38a is required for colorectal cancer cell homeostasis as the inhibition of its kinase function by pharmacological blockade or genetic inactivation causes cell cycle arrest, autophagy and cell death in a cell type-specific manner. Deficiency of p38a activity induces a tissue-restricted upregulation of the GABARAP gene, an essential component of autophagic vacuoles and autophagosomes, whereas simultaneous inhibition of autophagy significantly increases cell death by triggering apoptosis. These data identify p38a as a central mediator of colorectal cancer cell homeostasis and establish a rationale for the evaluation of the pharmacological manipulation of the p38a pathway in the treatment of colorectal cancer. Colorectal cancer is a major health concern, with more than 1 000 000 new cases and 500 000 deaths expected worldwide per year.1 Prognostic evaluation is currently based on histological appearance, and there are no molecular markers internationally recognized as standard predictor factors. The conventional therapy involving surgery and adjuvant therapy seems to give rise to improvements in progression-free and overall survival. Nevertheless about 50% of patients die within 5 years owing to metastasis or recurrent disease.2 The prospects for further substantial advances in the management of colorectal cancer reside in a systematic genetic and functional dissection of cell cycle and cell death regulatory pathways in tumor cells in order to identify differential cellular effects of agents that may have a direct impact on cancer therapy.During the last decade, a number of deacetylase inhibitors (DI) have been identified. These DI induce tumor cells to undergo growth arrest, differentiation, and/or apoptosis in culture and in animal models, at doses that seem to be nontoxic and appear to be selective. Butyrate, a DI that is naturally formed in the human colon, is able to reduce the size and the number of tumors in rat models of bowel cancer.3 In vitro, sodium butyrate (NaB) is a potent differentiating agent for several colorectal cancer cell lines (CRCs).4-6 NaB-mediated cell cycle withdrawal of CRCs appears to be dependent on acetylation of histones and consequent changes in transcription, requiring continuous protein synthesis and the expression of p21. 7 It has recently been shown that 1 mM NaB is the best working concentration to activate the differentiation program in CRCs without triggering apoptosis, whereas 5 mM NaB is sufficient to induce a p53-independent...

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“…however, a recent study showed that dr3 may be a new receptor for E-selectin, which has been linked with cancer metastasis. The findings of this study indicate that the activation of dr3 in response to E-selectin triggers the transendothelial migration of cancer cells and protects them against apoptosis, suggesting that dr3 has evolved to provide metastatic advantages to colon cancer cells (13).…”

Section: Introductionmentioning

confidence: 76%

Aberrant expression and function of death receptor-3 and death decoy receptor-3 in human cancer

Sanders

et al. 2011

Experimental and Therapeutic Medicine

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Abstract. death receptor-3 (dr3) and death decoy receptor-3 (dcr3) are both members of the tumour necrosis factor receptor (tnFr) superfamily. the tnFr superfamily contains eight death domain-containing receptors, including tnFr1 (also called dr1), Fas (also called dr2), dr3, dr4, dr5, dr6, nGFr and Edar. upon the binding of these receptors with their corresponding ligands, the death domain recruits various proteins that mediate both the death and proliferation of cells. receptor function is negatively regulated by decoy receptors (dcr1, dcr2, dcr3 and OpG). dr3/dcr3 are a pair of positive and negative players with which vascular endothelial growth inhibitor (VEGi) interacts. VEGi has been suggested to be a potential tumour suppressor. the inhibitory effects of VEGi on cancer are manifested in three main areas: a direct effect on cancer cells, an anti-angiogenic effect on endothelial cells, and the stimulation of dendritic cell maturation. a recent study indicated that dr3 may be a new receptor for E-selectin, which has been reported to be associated with cancer metastasis. dcr3 is a soluble receptor, highly expressed in various tumours, which lacks an apparent transmembrane segment, prevents cytokine response through ligand binding and neutralization, and is an inhibitor of apoptosis. dcr3 serves as a decoy receptor for Fasl, liGht and VEGi. the cytokine liGht activates various anti-tumour functions and is expected to be a promising candidate for cancer therapy. certain tumours may escape Fasl-dependent immunecytotoxic attack by expressing dcr3, which blocks Fasl function. dr3/dcr3 play profound roles in regulating cell death and proliferation in cancer. The present review briefly discusses dr3/dcr3 and attempts to elucidate the role of these negative and positive players in cancer.

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Death Receptor-3, a New E-Selectin Counter-Receptor that Confers Migration and Survival Advantages to Colon Carcinoma Cells by Triggering p38 and ERK MAPK Activation

Cited by 93 publications

References 46 publications

Regulation of Sialyl Lewis Antigen Expression in Colon Cancer Cells by Sialidase NEU4

Regulation of Sialyl Lewis Antigen Expression in Colon Cancer Cells by Sialidase NEU4

A novel cell type-specific role of p38α in the control of autophagy and cell death in colorectal cancer cells

Aberrant expression and function of death receptor-3 and death decoy receptor-3 in human cancer

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