Caveolin‐1 up‐regulates integrin α2,6‐sialylation to promote integrin α5β1‐dependent hepatocarcinoma cell adhesion

Yu, Shengjin; Fan, Jianhui; Liu, Linhua; Zhang, Lijun; Wang, Shujing; Zhang, Jianing

doi:10.1016/j.febslet.2013.02.002

Cited by 44 publications

(34 citation statements)

References 33 publications

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“…However, as has been seen in several solid malignancies, [20][21][22][23] there is accruing evidence that altered glycosylation is important in MM. [24][25][26] We were particularly interested in identifying alterations in glycosylation with the potential to impact cell trafficking in MM, given the crucial role that this process is known to play in cell-cell interactions and hematogenous metastasis of cancer cells.…”

Section: Discussionmentioning

confidence: 99%

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The sialyltransferase ST3GAL6 influences homing and survival in multiple myeloma

Glavey

Manier

Natoni

et al. 2014

Blood

105

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Key Points• Knockdown of the sialyltransferase, ST3GAL6, in MM inhibits in vivo homing and prolongs survival in xenograft mice.• In MM patients, high expression of ST3GAL6 is associated with inferior overall survival.Glycosylation is a stepwise procedure of covalent attachment of oligosaccharide chains to proteins or lipids, and alterations in this process, especially increased sialylation, have been associated with malignant transformation and metastasis. The role of altered sialylation in multiple myeloma (MM) cell trafficking has not been previously investigated.In the present study we identified high expression of b-galactoside a-2,3-sialyltransferase, ST3GAL6, in MM cell lines and patients. This gene plays a key role in selectin ligand synthesis in humans through the generation of functional sialyl Lewis X. In MRC IX patients, high expression of this gene is associated with inferior overall survival. In this study we demonstrate that knockdown of ST3GAL6 results in a significant reduction in levels of a-2,3-linked sialic acid on the surface of MM cells with an associated significant reduction in adhesion to MM bone marrow stromal cells and fibronectin along with reduced transendothelial migration in vitro. In support of our in vitro findings, we demonstrate significantly reduced homing and engraftment of ST3GAL6 knockdown MM cells to the bone marrow niche in vivo, along with decreased tumor burden and prolonged survival. This study points to the importance of altered glycosylation, particularly sialylation, in MM cell adhesion and migration. (Blood. 2014;124(11):1765-1776

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Section: Discussionmentioning

confidence: 99%

“…4,21,22 Studies of selectins and their ligands have highlighted the importance of posttranslational glycosylation in the process of leukocyte tethering, rolling, and For personal use only. on May 10, 2018. by guest www.bloodjournal.org From transendothelial migration, which are central to cellular trafficking.…”

Section: Discussionmentioning

confidence: 99%

The sialyltransferase ST3GAL6 influences homing and survival in multiple myeloma

Glavey

Manier

Natoni

et al. 2014

Blood

105

View full text Add to dashboard Cite

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“…The same concerns the influence of on cellular motility and invasive capabilities. For particular cell types overexpression of a-2,6-GalSA or a-2,6-ST enzyme has been associated with enhanced tumor migration potential (breast cancer cell line [22], colon cancer cell lines [23], HCC cell line [24]), whereas for other cell types this phenomenon results in impaired departure from the originating tissue (lymphosarcoma cell line MDAY-D2 [25]) and inhibition of tumor growth in vivo (glioma [26]). …”

Section: Discussionmentioning

confidence: 99%

The presence and clinical implications of α-2,6-galactose-linked sialic acids in non-small-cell lung cancer brain metastases — preliminary study

Pelak

Jarosz

Strączyńska-Niemiec

et al. 2014

Folia Histochem Cytobiol.

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Brain metastases (BM) in non-small-cell lung cancer (NSCLC) patients present an increasing clinical challenge. Identifying biomarkers which specifically identify patients at high risk of BM may improve their early diagnosis, which is crucial for surgical and radiotherapeutic treatment outcome. Alpha-2,6-sialyltransferase (a-2,6-ST) and the primary product of its activity, alpha-2,6-galactose-linked sialic acids (a-2,6-GalSA) have been found responsible for the adhesion of tumor cells to the brain vessels' endothelium and enabling their transmigration through the blood-brain barrier in brain metastatic tumors. The aim of the study was to investigate by histochemical method the presence and possible role of a-2,6-GalSA in the formation of brain metastasis in NSCLC. In the screening phase 76 metastatic brain tumors were stained for a-2,6-GalSA and the second phase involved an identical staining of 20 primary tumors of patients who had their primary tumors treated with surgery or definite radiochemotherapy yet who later developed BM. The results were compared to a control group of 22 patients treated with surgery for NSCLC and who survived 5 years without the recurrence of disease. Alpha-2,6-GalSA presence was found to be down-regulated in poorly differentiated tumor types, whereas majority of differentiated tumors overexpressed it. This was statistically significant for both BM and the primary tumors. The expression of a-2,6-GalSA remained stable in primary and metastatic tumor pairs, however, no statistically significant differences were observed between study and control groups. Within the study group, a higher a-2,6-GalSA expression was associated with better overall survival, but not all statistical models found this result significant. Further studies are recommended to validate these findings.

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“…As a scaffolding protein, caveolin containing cholesterol and glycosphingolipid components within the plasma membranes mediates processes such as caveolae biogenesis, transmembrane transport, signal transduction, and tumorgenesis [88]. Intriguingly, its role in regulating the conversion of LG-CD147 to HG-CD147 is inconsistent.…”

Section: Proteins Regulating the Glycosylation Of Cd147mentioning

confidence: 99%

Importance of N-Glycosylation on CD147 for Its Biological Functions

Bai

Huang

et al. 2014

IJMS

101

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Glycosylation of glycoproteins is one of many molecular changes that accompany malignant transformation. Post-translational modifications of proteins are closely associated with the adhesion, invasion, and metastasis of tumor cells. CD147, a tumor-associated antigen that is highly expressed on the cell surface of various tumors, is a potential target for cancer diagnosis and therapy. A significant biochemical property of CD147 is its high level of glycosylation. Studies on the structure and function of CD147 glycosylation provide valuable clues to the development of targeted therapies for cancer. Here, we review current understanding of the glycosylation characteristics of CD147 and the glycosyltransferases involved in the biosynthesis of CD147 N-glycans. Finally, we discuss proteins regulating CD147 glycosylation and the biological functions of CD147 glycosylation.

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Caveolin‐1 up‐regulates integrin α2,6‐sialylation to promote integrin α5β1‐dependent hepatocarcinoma cell adhesion

Cited by 44 publications

References 33 publications

The sialyltransferase ST3GAL6 influences homing and survival in multiple myeloma

The sialyltransferase ST3GAL6 influences homing and survival in multiple myeloma

The presence and clinical implications of α-2,6-galactose-linked sialic acids in non-small-cell lung cancer brain metastases — preliminary study

Importance of N-Glycosylation on CD147 for Its Biological Functions

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