Mass spectrometry-based N-linked glycomic profiling as a means for tracking pancreatic cancer metastasis

Park, Haemin; Hwang, Mintai P.; Kim, Yoon-Woo; Kim, Kyoung-Jin; Jin, Jang Mi; Kim, Young Hwan; Yang, Yung‐Hun; Lee, Kwan H.; Kim, Yun‐Gon

doi:10.1016/j.carres.2015.04.019

Cited by 46 publications

(33 citation statements)

References 35 publications

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“…As MALDI-TOP MS has been used to effectively profile glycans in cancer, 22 we expect that this method should be adaptable for N -glycan analysis in breast cancer tissues and cells. In this study, we revealed marked differences of N -glycans in breast cancer tissues, adjacent tissues and MDA-MB-231 and MCF-10A cells by MS analysis.…”

Section: Discussionmentioning

confidence: 99%

Functional roles of sialylation in breast cancer progression through miR-26a/26b targeting ST8SIA4

Dong

et al. 2016

Cell Death Dis

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Sialylation is one of the altered glycosylation patterns associated with cancer progression. In this study, we investigated the N-glycan profiles of breast cancer patients and cell lines to reveal sialylation associated with breast cancer progression, and provided new evidences of miRNA-mediated sialylation. MALDI-TOF MS analysis revealed that N-glycans found in breast cancer tissues and breast cancer cell MDA-MB-231 featured increased levels of sialylation compared with adjacent tissues and normal breast epithelial cell MCF-10A. The expressional profiles of 20 sialyltransferase genes were then analyzed and found significantly different comparing breast cancer samples with adjacent tissues, and two breast cancer cell lines MDA-MB-231 and MCF-7 with different metastatic potential and MCF-10A cells. Tumor tissues and highly metastatic breast cancer cell line MDA-MB-231 exhibited higher levels of ST8SIA4. Knocking down ST8SIA4 in breast cancer cell lines significantly inhibited their malignant behaviors including cell proliferation and invasion in a sialyltransferase-dependent manner. By applying bioinformatic approaches for the prediction of miRNA targeting 3′-UTR of ST8SIA4, we identified ST8SIA4 as one of the miR-26a/26b-targeted genes. Further data analysis revealed the inversely related expression of ST8SIA4 and miR-26a/26b in breast cancer cells, tumor tissues and corresponding adjacent tissues. The ability of miR-26a/26b to interact specifically with and regulate the 3′-UTR of ST8SIA4 was demonstrated via a luciferase reporter assay. The forced expression of miR-26a/26b was able to induce a decrease of ST8SIA4 level and also to affect breast cancer cells progression, while altered expression of ST8SIA4 in breast cancer cells modulated progression upon transfection with miR-26a/26b mimics or inhibiter. Taken together, these results indicate that changes in the glycosylation patterns and sialylation levels may be useful markers of the progression of breast cancer, as well as miR-26a/26b may be widely involved in the regulation of sialylation machinery by targeting ST8SIA4.

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Section: Discussionmentioning

confidence: 99%

Functional roles of sialylation in breast cancer progression through miR-26a/26b targeting ST8SIA4

Dong

et al. 2016

Cell Death Dis

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“…Several studies have demonstrated that changes in glycosylation promote tumor development and metastasis (Li, Wang, Tan, Chen, & Guan, ; Munkley & Elliott, ; Munkley, Mills, & Elliott, ; Potapenko et al, ). Indeed, changes in the process of N‐glycosylation in tumor cells, such as the synthesis of highly branched glycans, are among the factors that determine the metastatic potential of tumor cells (Asada, Furukawa, Segawa, Endo, & Kobata, ; Nakahara & Raz, ; Park et al, ). β1 Integrin is an N‐glycosylated protein and its activity is regulated by glycosylation (Janik, Litynska, & Vereecken, ).…”

Section: Introductionmentioning

confidence: 99%

sp²‐Iminosugar α‐glucosidase inhibitor 1‐C‐octyl‐2‐oxa‐3‐oxocastanospermine specifically affected breast cancer cell migration through Stim1, β1‐integrin, and FAK signaling pathways

Gueder¹,

Allan²,

Telliez³

et al. 2017

Journal Cellular Physiology

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Aberrant glycosylation changes on many glycoproteins are often related to cancer progression and metastasis. sp -Iminosugar-type castanospermine analogues, inhibitors of α-glucosidases, have been reported to exhibit antitumor activity. However, their effects on cell migration and the underlying molecular mechanism are not fully understood. Here, we investigated the effect of the pseudo-C-octyl glycoside 2-oxa-3-oxocastanospermine derivatives (CO-OCS) on breast cancer cells (MCF-7 and MDA-MB-231 cells), and MCF-10A mammary normal cell lines. We showed that CO-OCS treatment results in the drastic decrease of breast cancer cell migration without affecting cell proliferation. Furthermore, CO-OCS significantly reduced both the expression of β1-integrin, which is a crucial interacting partner of Focal Adhesion Kinase (FAK), and the phosphorylation rates of FAK and ERK1/2. CO-OCS also drastically reduced Ca entry through Store Operated Channels (SOC). Orai1 and Stim1, two N-glycosylated proteins, are involved in Store-Operated Calcium Entry (SOCE), and are essential for breast tumor cell migration. Our results showed that CO-OCS decreased the expression, at the protein level, of Stim1 without affecting that of Orai1. Moreover, cell migration and SOCE were attenuated by CO-OCS as well as when Stim1 was silenced. In contrast, in MCF-10A cells, CO-OCS slightly reduced cell migration, but was without effect on gene expression of Stim1, Orai1, β1-integrin, or FAK and ERK1/2 activation. Our results provide strong evidence for a significant effect of CO-OCS on breast cancer cell migration and support that this effect was associated with β1-integrin, Stim1, and FAK signaling pathways.

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“…This has been seen with the smoking and lung cancer-induced changes in N-glycosylation of serum proteins, 238 ovarian cancer, 239,240 metastatic pancreatic cancer, 241 predictions in castration-resistant prostate cancer, 242 and breast cancer. 243 Because of a very extensive number of isomeric possibilities, this area appears to be among the most challenging in the field of glycoanalysis and a wider variety of authentic standards are still needed to push this area forward.…”

Section: Selected Applicationsmentioning

confidence: 96%

Recent Advances in the Analysis of Complex Glycoproteins

et al. 2016

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Mass spectrometry-based N-linked glycomic profiling as a means for tracking pancreatic cancer metastasis

Cited by 46 publications

References 35 publications

Functional roles of sialylation in breast cancer progression through miR-26a/26b targeting ST8SIA4

Functional roles of sialylation in breast cancer progression through miR-26a/26b targeting ST8SIA4

sp²‐Iminosugar α‐glucosidase inhibitor 1‐C‐octyl‐2‐oxa‐3‐oxocastanospermine specifically affected breast cancer cell migration through Stim1, β1‐integrin, and FAK signaling pathways

Recent Advances in the Analysis of Complex Glycoproteins

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Mass spectrometry-based N-linked glycomic profiling as a means for tracking pancreatic cancer metastasis

Cited by 46 publications

References 35 publications

Functional roles of sialylation in breast cancer progression through miR-26a/26b targeting ST8SIA4

Functional roles of sialylation in breast cancer progression through miR-26a/26b targeting ST8SIA4

sp2‐Iminosugar α‐glucosidase inhibitor 1‐C‐octyl‐2‐oxa‐3‐oxocastanospermine specifically affected breast cancer cell migration through Stim1, β1‐integrin, and FAK signaling pathways

Recent Advances in the Analysis of Complex Glycoproteins

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Product

Resources

About

sp²‐Iminosugar α‐glucosidase inhibitor 1‐C‐octyl‐2‐oxa‐3‐oxocastanospermine specifically affected breast cancer cell migration through Stim1, β1‐integrin, and FAK signaling pathways