ST6GalNAcII mediates the invasive properties of breast carcinoma through PI3K/Akt/NF‐κB signaling pathway

Ren, Dongliang; Li, Jia; Li, Yanyan; Gong, Yanxin; Liu, Chen; Zhang, Xu; Wang, Ning; Zhao, Yongfu

doi:10.1002/iub.1268

Cited by 22 publications

(21 citation statements)

References 25 publications

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“…Mounting evidence demonstrated that the alterations of sialylation and the levels of ST activities derived from cancer cells were relevant to breast cancer invasion and metastasis. 28, 29 Here, we indicated that the ST profiling patterns were significantly different in breast cancer tissues to adjacent tissues. Among these, the expression of ST6GALNAC5 , ST8SIA3 and ST8SIA4 was significantly upregulated in breast cancer tissues compared with adjacent tissues, and ST8SIA2 and ST8SIA6 were upregulated in the adjacent tissues.…”

Section: Discussionmentioning

confidence: 74%

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: 74%

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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“…As proved, p-Akt 308 and p-Akt 473, the phosphorylation of Akt, promoted tumor invasion and chemoresistance of breast carcinoma. 38, 39 In this article, when siAkt was utilized to inhibit the expression of p-Akt 308 and p-Akt 473 in breast cancer, the capability of cell migration, invasion and proliferation was significantly attenuated, indicating that the phosphorylation of Akt did have a role in the progression of breast cancer. Taken together, miR-106b and miR-93 mediated cell migration, invasion and proliferation by suppression of PTEN via PI3K/Akt pathway in breast cancer.…”

Section: Discussionmentioning

confidence: 86%

MiR-106b and miR-93 regulate cell progression by suppression of PTEN via PI3K/Akt pathway in breast cancer

et al. 2017

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Accumulating evidences have revealed that dysregulated microRNAs (miRNAs) involve in the tumorigenesis, progression and even lead to poor prognosis of various carcinomas, including breast cancer. MiRNA-106b-5p (miR-106b) and miRNA-93-5p (miR-93) levels were confirmed to be significantly upregulated in breast cancer clinical samples (n=36) and metastatic cell line (MDA-MB-231) compared with those in the paired adjacent tissues and normal breast epithelial cell line (MCF-10A). Moreover, further research stated that the capability of migration, invasion and proliferation changed along with the altered expression of miR-106b and miR-93 in breast cancer. PTEN, the tumor-suppressor gene, was discovered to be reduced in breast cancer tissues or MDA-MB-231 cells with high levels of miR-106b and miR-93, which were inversely expressed in PTEN overexpression tissues or cells. Based on the investigation, miR-106b and miR-93 induced the migration, invasion and proliferation and simultaneously enhanced the activity of phosphatidylinositol-3 kinase (PI3K)/Akt pathway of MCF-7 cells, which could be blocked by upregulation of PTEN. Furthermore, suppression of PTEN reversed the function induced by anti-miR-106b and anti-miR-93 in MDA-MB-231 cells, indicating that PTEN was directly targeted by these miRNAs and acted as the potential therapeutic target for breast cancer therapy. In short, reductive PTEN mediated by miR-106b and miR-93 promoted cell progression through PI3K/Akt pathway in breast cancer.

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“…Changes in cell surface glycosylation have been shown to increase tumorigenesis and metastasis (Ohtsubo and Marth, 2006; Ren et al, 2014; Tamura et al, 2014; Tarp and Clausen, 2008; Taylor-Papadimitriou et al, 1999). The most prevalent aberrant glycoforms found in cancer are the Tn (GalNAc α 1-O-Ser/Thr) and sialyl-Tn (STn) (NeuAc α 2-6-GalNAc α 1-O-Ser/Thr) glycoforms (Springer, 1984).…”

Section: Introductionmentioning

confidence: 99%

“…Hypoxic conditions often found in tumors might alter expression of glycosyltransferases (Kannagi et al, 2010), including sialyltransferases such as ST6GalNAcI to create sialyl-Tn antigens. Glycosylation changes also alter cell adhesion and motility, which increase the metastatic potential of the tumor cell (Gill et al, 2013; Radhakrishnan et al, 2014; Ren et al, 2014; Tamura et al, 2014). Tn and STn antigen expression is correlated with adverse outcome and decreased patient survival in breast cancer, gastric cancer, endometrial cancer, and oral squamous cell carcinoma, among other cancers (Cazet et al, 2010; Itzkowitz, 2003; Lin et al, 2014; Ohno et al, 2006; Victorzon et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

Engineered CAR T Cells Targeting the Cancer-Associated Tn-Glycoform of the Membrane Mucin MUC1 Control Adenocarcinoma

et al. 2016

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SUMMARY Genetically modified T cells expressing chimeric antigen receptors (CARs) demonstrate robust responses against lineage restricted, non-essential targets in hematologic cancers. However, in solid tumors, the full potential of CAR T cell therapy is limited by the availability of cell surface antigens with sufficient cancer-specific expression. The majority of CAR targets have been normal self-antigens on dispensable hematopoietic tissues or overexpressed shared antigens. Here, we established that abnormal self-antigens can serve as targets for tumor rejection. We developed a CAR that recognized cancer-associated Tn glycoform of MUC1, a neoantigen expressed in a variety of cancers. Anti-Tn-MUC1 CAR T cells demonstrated target-specific cytotoxicity and successfully controlled tumor growth in xenograft models of T cell leukemia and pancreatic cancer. These findings demonstrate the therapeutic efficacy of CAR T cells directed against Tn-MUC1 and present aberrantly glycosylated antigens as a novel class of targets for tumor therapy with engineered T cells.

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ST6GalNAcII mediates the invasive properties of breast carcinoma through PI3K/Akt/NF‐κB signaling pathway

Cited by 22 publications

References 25 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

MiR-106b and miR-93 regulate cell progression by suppression of PTEN via PI3K/Akt pathway in breast cancer

Engineered CAR T Cells Targeting the Cancer-Associated Tn-Glycoform of the Membrane Mucin MUC1 Control Adenocarcinoma

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