Chondroitin sulfate–mediated N-cadherin/β-catenin signaling is associated with basal-like breast cancer cell invasion

Nadanaka, Satomi; Kinouchi, Hiroki; Kitagawa, Hiroshi

doi:10.1074/jbc.m117.814509

Cited by 56 publications

(64 citation statements)

References 57 publications

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“…Notably, site-specific sulfation of CSs regulates invasion of cancer cells via the N-cadherin/β-catenin pathway. 47 Low levels of CS chains in the extracellular matrix of colorectal cancer reduce the expression of vimentin and snail family transcriptional repressor 1 (SNAI1), and increase the expression of E-cadherin. 46 Expression of the stem cell marker CD44 is increased in the mesenchymal subsets of gliomas and is closely related to EMT.…”

Section: Discussionmentioning

confidence: 99%

Expression and function of chondroitin 4‐sulfate and chondroitin 6‐sulfate in human glioma

et al. 2019

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Key molecules promoting migration and invasion exist in the extracellular matrix, and include chondroitin 4‐sulfate (C4S) and chondroitin 6‐sulfate (C6S), functionally important carbohydrate chains of chondroitin sulfate proteoglycans that participate in regulating cancer development. Here, we show that C4S and C6S expression is upregulated in human glioma tissues, when compared to normal brain tissue, and that the extent of upregulation positively correlated with glioma malignancy. Treatment of cultured glioma cells with C4S and C6S enhanced cell viability, migration, and invasion, increased MMP‐2 and MMP‐9 levels, enhanced N‐cadherin, but reduced E‐cadherin expression. Inhibition of expression of the two CS synthetic enzymes chondroitin 4‐O‐sulfotransferase‐1 (C4ST‐1/CHST11) and chondroitin 6‐O‐sulfotransferase‐1 (C6ST‐1/CHST3) suppressed cell viability, migration and invasion, reduced MMP‐2 and MMP‐9 expression, and reduced N‐cadherin expression, but increased E‐cadherin levels. The C4S‐ and C6S‐enhanced epithelial‐to‐mesenchymal transition and expression of MMP‐2 occurred via activation of the PI3K/AKT signaling pathway, known to be involved in promoting cell migration and invasion. In immune‐deficient larval zebrafish, C4S and C6S increased the numbers of viable tumor cells, thereby promoting glioma cell proliferation. The present observations point to a novel role of C4S and C6S in human glioma cell functions, thus possibly representing targets in glioma therapy.

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Section: Discussionmentioning

confidence: 99%

Expression and function of chondroitin 4‐sulfate and chondroitin 6‐sulfate in human glioma

et al. 2019

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“…Human placental pericyte glycolytic activity is inversely associated with the expression level of N-cadherin (Cantelmo et al, 2016). It has been shown that N-cadherin sequesters β-catenin to the plasma membrane, which may lower β-catenin-dependent promotion of proliferation as was shown to occur in tumor cells (Nadanaka et al, 2018). This effect may be mediated through the regulation of metabolic pathways since c-Myc, a major target gene of the β-catenin/TCF transcription factor complex, is a well-established effector of glycolysis (Li and Wang, 2008).…”

Section: Quiescencementioning

confidence: 99%

Metabolic Coordination of Pericyte Phenotypes: Therapeutic Implications

Nwadozi

Rudnicki

Haas

2020

Front. Cell Dev. Biol.

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Pericytes are mural vascular cells found predominantly on the abluminal wall of capillaries, where they contribute to the maintenance of capillary structural integrity and vascular permeability. Generally quiescent cells in the adult, pericyte activation and proliferation occur during both physiological and pathological vascular and tissue remodeling. A considerable body of research indicates that pericytes possess attributes of a multipotent adult stem cell, as they are capable of self-renewal as well as commitment and differentiation into multiple lineages. However, pericytes also display phenotypic heterogeneity and recent studies indicate that lineage potential differs between pericyte subpopulations. While numerous microenvironmental cues and cell signaling pathways are known to regulate pericyte functions, the roles that metabolic pathways play in pericyte quiescence, self-renewal or differentiation have been given limited consideration to date. This review will summarize existing data regarding pericyte metabolism and will discuss the coupling of signal pathways to shifts in metabolic pathway preferences that ultimately regulate pericyte quiescence, self-renewal and trans-differentiation. The association between dysregulated metabolic processes and development of pericyte pathologies will be highlighted. Despite ongoing debate regarding pericyte classification and their functional capacity for trans-differentiation in vivo, pericytes are increasingly exploited as a cell therapy tool to promote tissue healing and regeneration. Ultimately, the efficacy of therapeutic approaches hinges on the capacity to effectively control/optimize the fate of the implanted pericytes. Thus, we will identify knowledge gaps that need to be addressed to more effectively harness the opportunity for therapeutic manipulation of pericytes to control pathological outcomes in tissue remodeling.

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“…Overexpression of Twist and β-catenin is associated with EMT and invasiveness [92][93][94]. Actin re-organization and the formation of stress fibers are essential events for cell migration, and are considered the hallmark of EMT [95,96].…”

Section: Discussionmentioning

confidence: 99%

Leptin promotes expression of EMT-related transcription factors and invasion in a Src and FAK-dependent pathway in MCF10A mammary epithelial cells

Olea-Flores

Zuñiga-Eulogio

Tacuba-Saavedra

et al. 2019

Preprint

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Leptin is one of the main adipokines secreted in breast tissue, and has been associated with epithelial-mesenchymal transition (EMT) and tumor progression in breast cancer. Leptin promotes EMT, cell migration and invasion in epithelial breast cells, leading to tumor progression. However, the molecular mechanism that underlies these events is not fully understood; however, the activation of different signaling pathways appears to be essential. In this sense, the effect of leptin on the activation of kinases like Src and FAK, which regulate signaling pathways that activate the EMT program, has not been completely described. Therefore, we investigated the involvement of these kinases using an in vitro model for leptin-induced EMT process in the non-tumorigenic MCF10A cell line. To this end, MCF10A cells were stimulated with leptin, and Src and FAK activation was assessed. Specific events occurring during EMT were also evaluated in the presence or absence of the kinases's chemical inhibitors PP2 and PF-573228. For instance, we tested the expression and subcellular localization of the EMT--catenin, by western blot and immunofluorescence. We also evaluated the secretion and activation of matrix metalloproteases (MMP-2 and MMP-9) by gelatin zymography. Invasiveness properties of leptin-stimulated cells were determined by invadopodia formation assays, and by the transwell chamber method. Our results showed that leptin promotes EMT through Src and FAK activation, which leads to the secretion and activation of MMP-2 and MMP-9, invadopodia formation and cell invasion in MCF10A cells. In conclusion, our data suggest that -catenin, the secretion of MMP-2, MMP-9, the invadopodia formation and invasion in MCF10A cells in a Src and FAK-dependent manner.

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Chondroitin sulfate–mediated N-cadherin/β-catenin signaling is associated with basal-like breast cancer cell invasion

Cited by 56 publications

References 57 publications

Expression and function of chondroitin 4‐sulfate and chondroitin 6‐sulfate in human glioma

Expression and function of chondroitin 4‐sulfate and chondroitin 6‐sulfate in human glioma

Metabolic Coordination of Pericyte Phenotypes: Therapeutic Implications

Leptin promotes expression of EMT-related transcription factors and invasion in a Src and FAK-dependent pathway in MCF10A mammary epithelial cells

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