Complex <i>N</i>-Glycan and Metabolic Control in Tumor Cells

Mendelsohn, Richard; Cheung, Pam; Berger, Lloyd C.; Partridge, Emily A.; Lau, Ken S.; Datti, Alessandro; Pawling, Judy; Dennis, James W.

doi:10.1158/0008-5472.can-06-4580

Cited by 51 publications

(35 citation statements)

References 47 publications

(56 reference statements)

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“…Finally, p53-but not p16-dependent cell senescence has been linked to the production of reactive oxygen species (ROS), notably in the context of normal endothelial cells (Cho et al, 2011), whereas tumor aggressiveness and neoangiogenesis can be both increased by Akt and/or NOX-1-induced ROS (Arbiser et al, 2002;Govindarajan et al, 2007). Therefore, ROS could be key mediators of the gal-1 opposite cell cycle regulation in cancer versus endothelial cells observed in the present study, especially when considering that galectins' expression or signaling has been associated with ROS production (Mendelsohn et al, 2007;Zhuravliova et al, 2009).…”

Section: Discussionmentioning

confidence: 66%

Galectin-1 in Melanoma Biology and Related Neo-Angiogenesis Processes

Mathieu

Lassalle

Toelen

et al. 2012

Journal of Investigative Dermatology

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Aggressiveness of advanced melanomas relates in part to their marked propensity to develop neoangiogenesis and metastases. Among its numerous pro-cancer roles, galectin (gal)-1 expressed and/or secreted by both cancer and endothelial cells stimulates proliferation and angiogenesis. This study first shows that gal-1 is more highly expressed at both mRNA and protein levels than its congeners in melanomas and particularly in advanced lesions. The roles of gal-1 were further investigated in vivo in the highly proliferating and vascularized pseudometastatic B16F10 mouse melanoma model using stable knockdown B16F10 cells and wild-type versus gal-1 knockout mice, and then in vitro in B16F10 tumoral and lung microvascular cells. Gal-1 depletion in the B16F10 tumor cells but not in the tumor-bearing mice significantly increased melanoma-bearing mice survival. Tumor-derived gal-1 thus seems to have more critical roles than the host-derived one. In fact, gal-1 displays distinct effects on the H-Ras-dependent p53/p21 pathways: in primary lung microvessel endothelial cells, gal-1 seems to be involved in the maintenance of senescent status through the induction of both p53 and p21 while it stimulates B16F10 cancer cell proliferation through a p53/p21 decrease. Altogether, these data point to gal-1 as a potential target to combat melanomas.

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Section: Discussionmentioning

confidence: 66%

Galectin-1 in Melanoma Biology and Related Neo-Angiogenesis Processes

Mathieu

Lassalle

Toelen

et al. 2012

Journal of Investigative Dermatology

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“…Likewise, increased protein N-glycosylation is linked to neoplasia (34,35). Previously, we showed that human OSCC specimens display aberrant amplification of the DPAGT1/canonical Wnt signaling positive feedback loop that leads to hyperglycosylation of E-cadherin and diminished intercellular adhesion (6).…”

Section: Discussionmentioning

confidence: 94%

N-Glycosylation Induces the CTHRC1 Protein and Drives Oral Cancer Cell Migration

Liu

Sengupta

Jamal

et al. 2013

Journal of Biological Chemistry

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Background: Increased protein N-glycosylation and aberrant Wnt signaling are features of oral cancer. Results: Overexpression of pro-migratory protein CTHRC1 is due to hyperglycosylation and transcriptional activation by canonical Wnt. Conclusion: N-Glycosylation collaborates with canonical Wnt to induce CTHRC1 and drive OSCC cell migration. Significance: Elucidating how N-glycosylation impacts tumor-promoting proteins is critical to understand cancer development and progression.

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“…6, 7). Previous works suggest that upon binding to glycans attached to GF receptors, oligomerized galectin-3 molecules crosslink GF receptors at the surface and delays their removal by endocytosis, resulting in prolongation of GF signaling (phosphorylation of Erk and nuclear translocation in cancer cells) (Partridge et al, 2004;Mendelsohn et al, 2007). Here, it is important to mention that our in vitro and in vivo results further support this view, suggesting that similar molecular mechanisms (galectin-3 interaction with IGF-R1) may be in-volved in IGF-1-mediated and injury-induced proliferation of microglia cell after ischemic injury.…”

Section: Discussionmentioning

confidence: 99%

Galectin-3 Is Required for Resident Microglia Activation and Proliferation in Response to Ischemic Injury

Lalancette–Hébert¹,

Swarup²,

Beaulieu³

et al. 2012

Journal of Neuroscience

232

247

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Growing evidence suggests that galectin-3 is involved in fine tuning of the inflammatory responses at the periphery, however, its role in injured brain is far less clear. Our previous work demonstrated upregulation and coexpression of galectin-3 and IGF-1 in a subset of activated/proliferating microglial cells after stroke. Here, we tested the hypothesis that galectin-3 plays a pivotal role in mediating injury-induced microglial activation and proliferation. By using a galectin-3 knock-out mouse (Gal-3KO), we demonstrated that targeted disruption of the galectin-3 gene significantly alters microglia activation and induces ϳ4-fold decrease in microglia proliferation. Defective microglia activation/proliferation was further associated with significant increase in the size of ischemic lesion, ϳ2-fold increase in the number of apoptotic neurons, and a marked deregulation of the IGF-1 levels. Next, our results revealed that contrary to WT cells, the Gal3-KO microglia failed to proliferate in response to IGF-1. Moreover, the IGF-1-mediated mitogenic microglia response was reduced by N-glycosylation inhibitor tunicamycine while coimmunoprecipitation experiments revealed galectin-3 binding to IGFreceptor 1 (R1), thus suggesting that interaction of galectin-3 with the N-linked glycans of receptors for growth factors is involved in IGF-R1 signaling. While the canonical IGF-1 signaling pathways were not affected, we observed an overexpression of IL-6 and SOCS3, suggesting an overactivation of JAK/STAT3, a shared signaling pathway for IGF-1/IL-6. Together, our findings suggest that galectin-3 is required for resident microglia activation and proliferation in response to ischemic injury.

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Complex N-Glycan and Metabolic Control in Tumor Cells

Abstract: Golgi B1,6N-acetylglucosaminyltransferase V (Mgat5) produces B1,6GlcNAc-branched complex N-glycans on cell surface glycoproteins that bind to galectins and promote surface residency of glycoproteins, including cytokine receptors.

Cited by 51 publications

References 47 publications

Galectin-1 in Melanoma Biology and Related Neo-Angiogenesis Processes

Galectin-1 in Melanoma Biology and Related Neo-Angiogenesis Processes

N-Glycosylation Induces the CTHRC1 Protein and Drives Oral Cancer Cell Migration

Galectin-3 Is Required for Resident Microglia Activation and Proliferation in Response to Ischemic Injury

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