Clinical Correlations of α2,6-Sialyltransferase Expression in Colorectal Cancer Patients

Lise, Mario; Belluco, Claudio; Perera, Sauni P.; Patel, Rupal; Thomas, Peter; Ganguly, Aniruddha

doi:10.1089/027245700429828

Cited by 63 publications

(45 citation statements)

References 17 publications

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“…Some authors reported the higher immunoreactivity of the enzyme a-2,6-sialyltransferase in well differentiated tumors (e.g. in hepatic cell carcinoma [21]), but others found the a-2,6-GalST immunoexpression to be more prevalent in tumors of higher histological grade (colorectal cancer [11], pancreatic cancer cell line [12]). The same concerns the influence of on cellular motility and invasive capabilities.…”

Section: Discussionmentioning

confidence: 99%

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The presence and clinical implications of α-2,6-galactose-linked sialic acids in non-small-cell lung cancer brain metastases — preliminary study

Pelak

Jarosz

Strączyńska-Niemiec

et al. 2014

Folia Histochem Cytobiol.

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Brain metastases (BM) in non-small-cell lung cancer (NSCLC) patients present an increasing clinical challenge. Identifying biomarkers which specifically identify patients at high risk of BM may improve their early diagnosis, which is crucial for surgical and radiotherapeutic treatment outcome. Alpha-2,6-sialyltransferase (a-2,6-ST) and the primary product of its activity, alpha-2,6-galactose-linked sialic acids (a-2,6-GalSA) have been found responsible for the adhesion of tumor cells to the brain vessels' endothelium and enabling their transmigration through the blood-brain barrier in brain metastatic tumors. The aim of the study was to investigate by histochemical method the presence and possible role of a-2,6-GalSA in the formation of brain metastasis in NSCLC. In the screening phase 76 metastatic brain tumors were stained for a-2,6-GalSA and the second phase involved an identical staining of 20 primary tumors of patients who had their primary tumors treated with surgery or definite radiochemotherapy yet who later developed BM. The results were compared to a control group of 22 patients treated with surgery for NSCLC and who survived 5 years without the recurrence of disease. Alpha-2,6-GalSA presence was found to be down-regulated in poorly differentiated tumor types, whereas majority of differentiated tumors overexpressed it. This was statistically significant for both BM and the primary tumors. The expression of a-2,6-GalSA remained stable in primary and metastatic tumor pairs, however, no statistically significant differences were observed between study and control groups. Within the study group, a higher a-2,6-GalSA expression was associated with better overall survival, but not all statistical models found this result significant. Further studies are recommended to validate these findings.

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Section: Discussionmentioning

confidence: 99%

“…Various studies have found a-2,6-GalSA to be associated with cell differentiation and proliferation [7], intercellular and cell-matrix interactions [8] and immunity [9]. Their role in cancer has not yet been fully established, although available studies tend to demonstrate it as an indicator of poor prognosis [10][11][12].…”

Section: Introductionmentioning

confidence: 99%

The presence and clinical implications of α-2,6-galactose-linked sialic acids in non-small-cell lung cancer brain metastases — preliminary study

Pelak

Jarosz

Strączyńska-Niemiec

et al. 2014

Folia Histochem Cytobiol.

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“…Columns, mean of four independent experiments done in duplicate; bars, SD. ST6Gal-I expression correlates with a poor prognosis in patients with colorectal and breast cancer (29,30). In vitro cell culture studies suggest that ST6Gal-I up-regulation may contribute to metastasis by regulating invasiveness and/or cell motility (31,32).…”

Section: Discussionmentioning

confidence: 99%

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

Seales¹,

et al. 2005

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Colon adenocarcinomas are known to express elevated levels of A2-6 sialylation and increased activity of ST6Gal-I, the Golgi glycosyltransferase that creates A2-6 linkages. Elevated ST6Gal-I positively correlates with metastasis and poor survival, and therefore ST6Gal-I-mediated hypersialylation likely plays a role in colorectal tumor invasion. Previously we found that oncogenic ras (present in roughly 50% of colon adenocarcinomas) up-regulates ST6Gal-I and, in turn, increases sialylation of B 1 integrin adhesion receptors in colon epithelial cells. However, we wanted to know if this pattern held true in vivo and, if so, how B 1 hypersialylation might contribute to colon tumor progression. In the present study, we find that B 1 integrins from colon adenocarcinomas consistently carry higher levels of A2-6 sialic acid. To explore the effects of increased A2-6 sialylation on B 1 -integrin function, we stably expressed ST6Gal-I in a colon epithelial cell line lacking endogenous ST6Gal-I. ST6Gal-I expressors (with A2-6 sialylated B 1 integrins) exhibited up-regulated attachment to collagen I and laminin and increased haptotactic migration toward collagen I, relative to parental cells (with completely unsialylated B 1 integrins). Blockade of ST6Gal-I expression with short interfering RNA reversed collagen binding back to the level of ST6Gal-I nonexpressors, confirming that a2-6 sialylation regulates B 1 integrin function. Finally, we show that B 1 integrins from ST6Gal-I expressors have increased association with talin, a marker for integrin activation. Collectively, these findings suggest that B 1 hypersialylation may augment colon tumor progression by altering cell preference for certain extracellular matrix milieus, as well as by stimulating cell migration. (Cancer Res 2005; 65(11): 4645-52)

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“…Increased levels of ST6Gal-I and α2,6-sialic acid have been observed in various cancer cells and are associated with a poor prognosis in cancer progression [11] . In vitro cell culture studies suggest that ST6Gal-I up-regulation may contribute to metastasis by regulating invasiveness and cell motility.…”

Section: Discussionmentioning

confidence: 99%

α2,6-hyposialylation of c-Met abolishes cell motility of ST6Gal-I-knockdown HCT116 cells

et al. 2009

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Aim: We aimed to investigate the potential modification of previously unrecognized surface glycoprotein(s) by α2,6-sialylation other than by integrins. Methods: The expression of β-galactoside α2,6-sialyltransferase (ST6Gal-I) in the colon cancer cell line HCT116 was reduced by siRNA. The adhesion and Boyden chamber assay were used to detect the variation in cell motility. α2,6-Sialylation proteins were detected with lectin affinity assay. The mRNA expression, protein expression and downstream signaling modulation with siRNA were detected using reverse transcription-polymerase chain reaction, flow cytometry analysis, and Western blot. Results: In HCT116 cells, the knockdown of ST6Gal-I inhibited cell motility, but did not affect cell adhesion. This selectively altered cell migration was caused by the loss of α2,6-sialic acid structures on c-Met. Moreover, STAT3 was dephosphorylated at tyrosine 705 in ST6Gal-I-knockdown (ST6Gal-I-KD) HCT116 cells. Conclusion: c-Met is the substrate of ST6Gal-I. The hyposialylation of c-Met can abolish cell motility in ST6Gal-I-KD HCT116 cells.

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Clinical Correlations of α2,6-Sialyltransferase Expression in Colorectal Cancer Patients

Cited by 63 publications

References 17 publications

The presence and clinical implications of α-2,6-galactose-linked sialic acids in non-small-cell lung cancer brain metastases — preliminary study

The presence and clinical implications of α-2,6-galactose-linked sialic acids in non-small-cell lung cancer brain metastases — preliminary study

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

α2,6-hyposialylation of c-Met abolishes cell motility of ST6Gal-I-knockdown HCT116 cells

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