Hypersialylation of β1 Integrins, Observed in Colon Adenocarcinoma, May Contribute to Cancer Progression by Up-regulating Cell Motility

Seales, Eric C.; Jurado, Gustavo Adolfo; Brunson, Brian; Wakefield, John K.; Frost, Andra R.; Bellis, Susan L.

doi:10.1158/0008-5472.can-04-3117

Cited by 298 publications

(278 citation statements)

References 46 publications

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“…Hypersialylation of β1 integrins can up-regulate cell motility in colon cancer. this increased negative charged properties of sialic acids was correlated with reduced adhesiveness of tumor cells and may be suitable for conformational change of integrin and enhances its function in cell-ecM interactions (33). similar studies have also indicated that increased sialylation could activate β1 integrin, mediate its adhesion to ecM proteins (34) and stimulating cell migration through host ecM (35).…”

Section: Discussionmentioning

confidence: 85%

Differential expression of the α2,3-sialic acid residues in breast cancer is associated with metastatic potential

Cui

Lin²,

Yue³

et al. 2011

Oncol Rep

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Abstract. Aberrant sialylation is closely associated with the malignant phenotype of cancer cells and metastatic potential. However, the precise nature of the molecules in breast cancers has not been unveiled. In this study, we investigated the expression levels of α2,3-sialic acid residues of 50 primary tumor cases, 50 pair-matched lymph node metastasis tumor samples and in the MDA-MB-231, t-47D and McF-7 breast cancer cell lines with different metastatic potential. the expression of α2,3-sialic acid residues was analyzed by histochemistry, cytochemistry and flow cytometry with Maackia amurensis lectin (MAl). the invasion and migration abilities of cells were examined using cell adhesion and transwell in vitro assays. pair-matched lymph node metastasis tumor samples exhibited higher levels of expression of α2,3-sialic acid residues compared to that of primary tumors (p=0.0432). Furthermore, of 38 tumors cases in t1/t2 stages, 31 (81.58%) had weak staining for MAL, which specifically binds to α2,3-sialic acid residues, whereas of 12 tumor cases in t3/t4 stages, only 1 (8.33%) had weak reactions for MAl. the highly metastatic breast cancer cell line MDA-MB-231 exhibited the strongest binding to MAl and the highest expression levels of α2,3-sialic acid residues among the selected cell lines, depending on mrnA expression levels of α2,3-sialyltransferase gene. the adhesion, invasion and migration activities confirmed that MDA-MB-231 exhibited the greater cell adhesion to, migration toward and invasion to Matrigel. taken together, the high expression of α2,3-sialic acid residues in breast cancer was associated with metastatic potential. this property may be important for developing new therapeutic approaches for breast cancer.

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Section: Discussionmentioning

confidence: 85%

Differential expression of the α2,3-sialic acid residues in breast cancer is associated with metastatic potential

Cui

Lin²,

Yue³

et al. 2011

Oncol Rep

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“…For example, GnT-V, GnT-III, ST6GalNAc I, and ST6Gal-I directly modify carbohydrate structures on ␤ 1 integrin and affect integrin activity. [33][34][35][36] These changes in N-glycosylation 33,37 or O-glycosylation 36 of ␤ 1 integrin lead to altered cell morphologic features and behavior. B4GALNT3 modifies N-and O-glycans decorated with GlcNAc in vitro.…”

Section: Discussionmentioning

confidence: 99%

B4GALNT3 Expression Predicts a Favorable Prognosis and Suppresses Cell Migration and Invasion via β1 Integrin Signaling in Neuroblastoma

Hsu

Che

Liao

et al. 2011

The American Journal of Pathology

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Neuroblastoma (NB) is the most common extracranial solid tumor in childhood, accounting for 8% to 10% of all pediatric malignancies. 1 This tumor arises from primitive neuroepithelial cells of the neural crest. 2 The behavior of NB is markedly heterogeneous, ranging from highly undifferentiated tumors with very poor outcomes to welldifferentiated benign ganglioneuroma or NB that may spontaneously regress with favorable prognosis. 3 Half of all patients with newly diagnosed NB are in a high-risk subset with poor overall survival despite intensive therapy. Therefore, it is important to develop useful prognostic tools and to understand NB pathogenesis to help design improved NB therapies.Glycosylation is regulated spatiotemporally during development of the nervous system. 4 Altered carbohydrate structures on tumors are often associated with tumor metastasis and progression. Tumor-associated carbohydrate epitopes commonly found in cancers include GM2,

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“…In vulva squamous carcinomas, b1-integrin is overexpressed and required for the invasive pattern (Brockbank et al, 2005). Interestingly, post-transcriptional modification of b1-integrin contributes to colon cancer progression (Seales et al, 2005). Mechanisms underlying modified integrin expression are still unclear, and possibly involve some oncogenes (Schwartz, 1993).…”

Section: Discussionmentioning

confidence: 99%

Cooperation between Myc and YY1 provides novel silencing transcriptional targets of α3β1-integrin in tumour cells

et al. 2006

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We show that human osteosarcoma cells (Saos-2) have downregulation of a3b1-integrin compared to normal bone cells; this was further described in human osteosarcomas and in a primary murine sarcoma. The a3 gene was silenced in Saos-2 cells causing a low expression of a3b1-integrin and reduction in collagen attachment with increasing migratory capacity. Chromatin immunoprecipitation assay performed on a3 promoter established that Myc and Yin Yang protein (YY1) cooperate in tandem to downregulate the a3 gene. This silencing mechanism involves the binding of Myc and YY1 to DNA and formation of complexes among Myc/Max, YY1, CREBbinding protein and deacetylation activity. The promoter containing deletions of E-boxes or YY1 cassettes failed to downregulate the transcription of a reporter gene as well as the inhibition of deacetylation activity. Overexpression of both Myc and YY1 was necessary to determine the a3-integrin promoter downregulation in normal osteoblasts. This downregulation of a3b1-integrin can contribute to the acquisition of a more aggressive phenotype. YY1 regulated negatively the Myc activity through a direct interaction with the Myc/Max and deacetylase complexes. This represents a novel silencing mechanism with broad implications in the transcription machinery of tumours.

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Hypersialylation of β1 Integrins, Observed in Colon Adenocarcinoma, May Contribute to Cancer Progression by Up-regulating Cell Motility

Cited by 298 publications

References 46 publications

Differential expression of the α2,3-sialic acid residues in breast cancer is associated with metastatic potential

Differential expression of the α2,3-sialic acid residues in breast cancer is associated with metastatic potential

B4GALNT3 Expression Predicts a Favorable Prognosis and Suppresses Cell Migration and Invasion via β1 Integrin Signaling in Neuroblastoma

Cooperation between Myc and YY1 provides novel silencing transcriptional targets of α3β1-integrin in tumour cells

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