α2,6-Sialylation promotes immune escape in hepatocarcinoma cells by regulating T cell functions and CD147/MMP signaling

Wang, Liping; Li, Shijun; Yu, Xiao; Han, Yang; Wu, Yinshuang; Wang, Shidan; Chen, Xixi; Zhang, Jianing

doi:10.1007/s13105-019-00674-8

Cited by 22 publications

(17 citation statements)

References 30 publications

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“…16,27 Furthermore, our lab previously reported that α2,6-sialylation can influence hepatocarcinoma cells proliferation. 18,23 To explore the functional characteristics of sialylated proteins in liver cancer cells of varying metastatic potential, MHCC-97H (a high-metastatic cell line) and HepG2 (a low-metastatic cell line) were investigated. A schematic of the procedure used to identify glycoproteins carrying α2,6-linked sialic acid is shown in Figure 1a.…”

Section: Identification Of Sialylated Proteins In Hepg2 and Mhcc-97h Samplesmentioning

confidence: 99%

“…16,17 We and others previously reported that α2,6-sialylation can influence tumor proliferation, immune responses, tumor-initiating potential, and the resistance to chemotherapy. [18][19][20] One such example includes the ST6Gal-I-mediated sialylation of the epidermal growth factor receptor (EGFR) that promotes EGFR activation and its resistance to gefitinib-mediated cell death in ovarian cancer cells. 20 Exosomes possess a specific protein, lipid, and glycan composition that regulates several important cellular pathways including membrane transport and fusion, the biogenesis of multivesicular bodies (MVB), tetraspanins, and tetraspanin-enriched microdomains (TEMs).…”

Section: Introductionmentioning

confidence: 99%

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Knockdown of ST6Gal‐I expression in human hepatocellular carcinoma cells inhibits their exosome‐mediated proliferation‐ and migration‐promoting effects

et al. 2021

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Abnormal sialylation is a distinctive feature of human hepatocellular carcinoma (HCC) and is closely related to its malignant properties. Exosomes have characteristic protein and lipid composition; however, the results concerning glycoprotein composition and glycosylation are scarce. In this study, liquid chromatography-tandem mass spectrometry (LC-MS/MS) identified multiple microvesicle-related sialylated proteins including CD63, a classic marker of exosomes. The silencing of α2,6-sialyltransferase I (ST6Gal-I) significantly reduced the levels of α2,6-sialylated glycoconjugates on CD63 and the surface of HCC-derived exosomes (HCCexo). And surface glycoconjugates play important roles in exosomes biogenesis and in their interaction with other cells. Compared to exosomes derived from naive HCC cells, α2,6-sialylation degradation abolished both the proliferation-promoting and migration-promoting effects of HCC-exo. Further analysis revealed that the Akt/GSK-3β or JNK1/2 signaling mediates HCC-exo-mediated proliferation in HCC cells, while ST6Gal-I silencing deactivated this pathway. These findings suggest that a loss of α2,6-sialylation decreases HCC progression through the loss of cancer cellderived exosomes; furthermore, it opens novel perspectives to further explore the functional role of glycans in the biology of exosomes.

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Section: Identification Of Sialylated Proteins In Hepg2 and Mhcc-97h Samplesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Knockdown of ST6Gal‐I expression in human hepatocellular carcinoma cells inhibits their exosome‐mediated proliferation‐ and migration‐promoting effects

et al. 2021

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“…Knockout of ST3GAL3 in melanoma cells reduced α-2,3 sialylation and the metastatic ability of these cells [ 90 ]. Furthermore, ST6GAL1 has been shown to promote immune escape in hepatocarcinoma cells by enhancing levels of CD147, MMP9, MMP2 and MMP7, and inhibiting T cell proliferation [ 91 ]. Lin and colleagues recently demonstrated that ST3GAL1-mediated O-linked sialylation of CD55, an important complement regulatory protein, acts like an immune checkpoint molecule for breast cancer cells to evade immune attack.…”

Section: Roles Of Sialyltransferases In Cancermentioning

confidence: 99%

Aberrant Sialylation in Cancer: Biomarker and Potential Target for Therapeutic Intervention?

Pietrobono¹,

Stecca²

2021

Cancers

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Sialylation is an integral part of cellular function, governing many biological processes including cellular recognition, adhesion, molecular trafficking, signal transduction and endocytosis. Sialylation is controlled by the levels and the activities of sialyltransferases on glycoproteins and lipids. Altered gene expression of these enzymes in cancer yields to cancer-specific alterations of glycoprotein sialylation. Mounting evidence indicate that hypersialylation is closely associated with cancer progression and metastatic spread, and can be of prognostic significance in human cancer. Aberrant sialylation is not only a result of cancer, but also a driver of malignant phenotype, directly impacting key processes such as tumor cell dissociation and invasion, cell-cell and cell-matrix interactions, angiogenesis, resistance to apoptosis, and evasion of immune destruction. In this review we provide insights on the impact of sialylation in tumor progression, and outline the possible application of sialyltransferases as cancer biomarkers. We also summarize the most promising findings on the development of sialyltransferase inhibitors as potential anti-cancer treatments.

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“…Abnormal cell surface sialylation is also involved in cancer development, including migration, invasion, metastasis, and immune escape. For example, ST6Gal1-mediated α2,6-sialylation promotes proliferation and migration of HCC through CD147/MMP signaling while inducing immune escape by inhibiting T cell proliferation via increased secretion of IL-10 and TGFβ1 [150]. Silencing of ST6GalNAc6 is induced by the NF-κB-mediated YY1/PRC2/EZH2 axis, which binds to its promoter and represses activity, leading to loss of immunosuppression and promotion of colorectal cancer progression [151].…”

Section: Sialylationmentioning

confidence: 99%

Association between Inflammation and Function of Cell Adhesion Molecules Influence on Gastrointestinal Cancer Development

Huang

Chang

Wang

et al. 2021

Cells

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Gastrointestinal cancer is highly associated with inflammatory processes inducing the release of cytokines from cancer or immune cells, including interferons, interleukins, chemokines, colony-stimulating factors, and growth factors, which promote or suppress tumor progression. Inflammatory cytokines within the tumor microenvironment promote immune cell infiltration. Infiltrating immune, and tumor-surrounding stromal cells support tumor growth, angiogenesis, metastasis, and immunosuppression through communication with inflammatory cytokines and cell adhesion molecules. Notably, infiltrating immune and tumor cells present immunosuppressive molecules, such as programmed death-ligand 1 (PD-L1) and CD80/CD86. Suppression of cytotoxic T cells promotes tumor avoidance of immune surveillance and greater malignancy. Moreover, glycosylation and sialylation of proteins hyperexpressed on the cancer cell surface have been shown to enhance immune escape and metastasis. Cytokine treatments and immune checkpoint inhibitors are widely used in clinical practice. However, the tumor microenvironment is a rapidly changing milieu involving several factors. In this review, we have provided a summary of the interactions of inflammation and cell adhesion molecules between cancer and other cell types, to improve understanding of the tumor microenvironment.

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α2,6-Sialylation promotes immune escape in hepatocarcinoma cells by regulating T cell functions and CD147/MMP signaling

Cited by 22 publications

References 30 publications

Knockdown of ST6Gal‐I expression in human hepatocellular carcinoma cells inhibits their exosome‐mediated proliferation‐ and migration‐promoting effects

Knockdown of ST6Gal‐I expression in human hepatocellular carcinoma cells inhibits their exosome‐mediated proliferation‐ and migration‐promoting effects

Aberrant Sialylation in Cancer: Biomarker and Potential Target for Therapeutic Intervention?

Association between Inflammation and Function of Cell Adhesion Molecules Influence on Gastrointestinal Cancer Development

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