Site-specific N-glycosylation of integrin α2 mediates collagen-dependent cell survival

Huang, Yen‐Lin; Liang, Ching-Yeu; Labitzky, Vera; Ritz, Danilo; Oliveira, Tiago; Cumin, Cécile; Estermann, Manuela; Lange, Tobias; Everest‐Dass, Arun; Jacob, Francis

doi:10.1016/j.isci.2021.103168

Cited by 13 publications

(9 citation statements)

References 49 publications

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“…Based on the exo-protein markers identi ed with the work ow we employed, we were able to narrow down the markers to seven proteins namely, ACSL4, IGSF8, ITGA2, ITGA5, ITGB3, MYOF and STX4. Previous studies on protein levels of these markers have shown that ACSL4, ITGA5 and STX4 are highly upregulated in ovarian cancer tissues [52][53][54] , while ITGA2 was upregulated in omental tumors 55 . High protein expression levels of ACSL4, ITGA2 and ITGA5 have been implicated in poor prognosis 52,53,56 ; however, the low expression of ITGB3 in HGSOC has been associated with favorable prognosis 57 .…”

Section: Discussionmentioning

confidence: 93%

Lineage specific extracellular vesicle-associated protein biomarkers for the early detection of high grade serous ovarian cancer

Trinidad

Pathak

Cheng

et al. 2023

Preprint

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High grade serous ovarian carcinoma (HGSOC) accounts for ~ 70% of ovarian cancer cases. Non-invasive, highly specific blood-based tests for pre-symptomatic screening in women are crucial to reducing the mortality associated with this disease. Since most HGSOCs typically arise from the fallopian tubes (FT), our biomarker search focused on proteins found on the surface of extracellular vesicles (EVs) released by both FT and HGSOC tissue explants and representative cell lines. Using mass spectrometry, 985 EV proteins (exo-proteins) were identified that comprised the FT/HGSOC EV core proteome. Transmembrane exo-proteins were prioritized because these could serve as antigens for capture and/or detection. With a nano-engineered microfluidic platform, six newly discovered exo-proteins (ACSL4, IGSF8, ITGA2, ITGA5, ITGB3, MYOF) plus a known HGSOC associated protein, FOLR1 exhibited classification performance ranging from 85–98% in a case-control study using plasma samples representative of early (including stage IA/B) and late stage (stage III) HGSOCs. Furthermore, by linear combination of IGSF8 and ITGA5 based on logistic regression analysis, we achieved a sensitivity of 80% (99.8% specificity). These lineage-associated exo-biomarkers have potential to detect cancer while localized to the FT when patient outcomes are more favorable.

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Section: Discussionmentioning

confidence: 93%

Lineage specific extracellular vesicle-associated protein biomarkers for the early detection of high grade serous ovarian cancer

Trinidad

Pathak

Cheng

et al. 2023

Preprint

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“…Moreover, we found that the methylation levels of 3 genes ( ITGA2 , CST9 , and ZIM2 ) in cfDNA are associated with the abovementioned imbalance of T-cell differentiation in this study. Integrin alpha 2 (ITGA2, CD49b) is the alpha subunit of a transmembrane receptor that mediates signal transduction within the cell–cell and cell–extracellular matrix (ECM) interactions, which play roles in various cell functions [ 27 , 28 ]. As a cell signal transduction receptor [ 29 , 30 ], ITGA2 forms T-cell immune synapses to activate T-cells and regulate their proliferation, cytokine secretion [ 31 ], and apoptosis [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

cfDNA Methylation Profiles and T-Cell Differentiation in Women with Endometrial Polyps

Niu

et al. 2022

Cells

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DNA methylation is a part of the regulatory mechanisms of gene expression, including chromatin remodeling and the activity of microRNAs, which are involved in the regulation of T-cell differentiation and function. However, the role of cfDNA methylation in T-cell differentiation is entirely unknown. In patients with endometrial polyps (EPs), we have found an imbalance of T-cell differentiation and an aberrant cfDNA methylation profile, respectively. In this study, we investigated the relationship between cfDNA methylation profiles and T-cell differentiation in 14 people with EPs and 27 healthy controls. We found that several differentially methylated genes (DMGs) were associated with T-cell differentiation in people with EPs (ITGA2-Naïve CD4, r = −0.560, p = 0.037; CST9-EMRA CD4, r = −0.626, p = 0.017; and ZIM2-CM CD8, r = 0.576, p = 0.031), but not in healthy controls (all p > 0.05). When we combined the patients’ characteristics, we found a significant association between ITGA2 methylation and polyp diameter (r = 0.562, p = 0.036), but this effect was lost when adjusting the level of Naïve CD4 T-cells (r = 0.038, p = 0.903). Moreover, the circulating sex hormone levels were associated with T-cell differentiation (estradiol-Naïve CD4, r = −0.589, p = 0.027), and the cfDNA methylation profile (testosterone-ZIM2, r = −0.656, p = 0.011). In conclusion, this study has established a link between cfDNA methylation profiles and T-cell differentiation among people with EPs, which may contribute to the etiology of EPs. Further functional studies are warranted.

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“…ST6Gal1 sialylation of β1 integrin in colon cancer also enhanced radio-resistance ( Lee et al, 2008 ). Furthermore, in the ovarian cancer line OVCAR4, ST6Gal1-mediated α2,6 sialylation was essential for integrin α2-dependent cancer cell survival ( Huang et al, 2021 ). In an in vivo model of mice mammary carcinoma, decreased cancer differentiation was observed with elevated ST6Gal1 and β1-integrin ( Hedlund et al, 2008 ).…”

Section: St6gal1 and Neoplastic Pathwaysmentioning

confidence: 99%

ST6Gal1: Oncogenic signaling pathways and targets

Bellis²,

Hjelmeland³

2022

Front. Mol. Biosci.

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The Golgi-sialyltransferase ST6Gal1 (βgalactosidase α2,6 sialyltransferase 1), adds the negatively charged sugar, sialic acid, to the terminal galactose of N-glycosylated proteins. Upregulation of ST6Gal1 is observed in many malignancies, and a large body of research has determined that ST6Gal1-mediated α2,6 sialylation impacts cancer hallmarks. ST6Gal1 affects oncogenic behaviors including sustained proliferation, enhanced self-renewal, epithelial-to-mesenchymal transition, invasion, and chemoresistance. However, there are relatively few ST6GaL1 related signaling pathways that are well-established to mediate these biologies: greater delineation of specific targets and signaling mechanisms that are orchestrated by ST6Gal1 is needed. The aim of this review is to provide a summary of our current understanding of select oncogenic signaling pathways and targets affected by ST6Gal1.

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Site-specific N-glycosylation of integrin α2 mediates collagen-dependent cell survival

Cited by 13 publications

References 49 publications

Lineage specific extracellular vesicle-associated protein biomarkers for the early detection of high grade serous ovarian cancer

Lineage specific extracellular vesicle-associated protein biomarkers for the early detection of high grade serous ovarian cancer

cfDNA Methylation Profiles and T-Cell Differentiation in Women with Endometrial Polyps

ST6Gal1: Oncogenic signaling pathways and targets

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