ライフサイエンスコーパス: ST6Gal I

1 beta-galactoside:alpha2-6-sialyltransferase (ST6Gal-I).

2 -galactosamide alpha-2,6-sialyltranferase I (ST6Gal-I).

3 beta-galactoside alpha2,6-sialyltransferase (ST6Gal-I).

4 tial for proper conformation and activity of ST6Gal I.

5 role of the S-sialylmotif of the same enzyme ST6Gal I.

6 and not on alpha2,6-sialic acids produced by ST6Gal-I.

7 ding is attenuated upon forced expression of ST6Gal-I.

8 ynthesized 13C-CMP-NeuAc to the desialylated ST6Gal-I.

9 lylation of these integrins with recombinant ST6Gal-I.

10 olon epithelial cell line lacking endogenous ST6Gal-I.

11 S2-013 and S2-LM7AA, which have upregulated ST6Gal-I.

12 lects for clonal variants with more abundant ST6Gal-I.

13 and GnT-II or trans-Golgi enzymes GalT-I and ST6Gal-I.

14 ST6Gal I, a glycosyltransferase expressed by B cells, ca

15 at the coordinate up-regulation of gal-3 and ST6Gal-I, a feature that is characteristic of colon carc

16 Correspondingly, ST6Gal-I activity augments the expression of tumor-promo

17 Intriguingly, differences in ST6Gal-I activity do not affect the function of DR4 or D

18 y and flow cytometry, we also show that high ST6Gal-I activity leads to sustained EGFR membrane reten

19 heroid growth, and clonal variants with high ST6Gal-I activity preferentially survived in CSC culture

20 s of variable thresholds, we found that high ST6Gal-I activity promotes increased integrin forces and

21 ated DNA damage, indicating that suppressing ST6Gal-I activity sensitizes inherently resistant cells

22 view summarizes the evidence suggesting that ST6Gal-I activity serves as an "off switch" for galectin

23 g TNFR1 at the cell surface via sialylation, ST6Gal-I acts as a functional switch to divert signaling

24 ST6Gal-I adds an alpha2,6-linked sialic acid to the term

25 The glycosyltransferase, ST6Gal-I, adds sialic acid in an alpha2-6 linkage to the

26 ST6Gal-I (alpha2,6-sialyltransferase) is expressed as tw

27 Sialylation of CD45 by the ST6Gal I also prevented galectin-1-induced clustering of

28 ST6Gal-I also augmented tumor-initiating potential.

29 ST6Gal-I also potentiates expression of the cell cycle r

30 ST6Gal-I also promoted resistance to gemcitabine and ena

31 ST6Gal-I, an enzyme upregulated in numerous malignancies

32 ST6Gal-I, an enzyme upregulated in numerous malignancies

33 precursor protein and the sialyltransferase ST6Gal I and is important in the pathogenesis of Alzheim

34 an nodes provided novel evidence for altered ST6Gal-I and GnT-IV glycotransferase activities in lung

35 c cancer cell line, which has low endogenous ST6Gal-I and limited metastatic potential, along with tw

36 ic cancer stem cells retained high levels of ST6Gal-I and resisted TNF-induced apoptosis, supporting

37 The mRNA expression levels of ST6GAL-I and SOX9 in human gastric epithelial cells corr

38 cans and by other sialyltransferases such as ST6Gal-I and ST6GalNAc-I, forming alpha2,6-sialylated co

39 helial monolayers expressed markedly reduced ST6Gal-I and underwent TNF-induced, caspase-mediated apo

40 y 50% of colon adenocarcinomas) up-regulates ST6Gal-I and, in turn, increases sialylation of beta1 in

41 e in the expression of the sialyltransferase ST6Gal I, and an increase in the expression of the galac

42 lation, we forced constitutive expression of ST6Gal-I, and found that this strongly inhibited PMA-ind

43 Together, these findings place ST6Gal-I as a critical player in imparting gemcitabine r

44 These findings indicate a role for ST6Gal-I as a mediator of tumor progression, with its ex

45 Recipient mice that received ST6Gal I(-/-) B cells demonstrated reduced influenza-spe

46 that in many ways carries an imprint of the ST6Gal-I binding site.

47 n gastric antral epithelium rarely expressed ST6Gal-I, but the number of ST6Gal-I-expressing epitheli

48 rum deprivation, supporting the concept that ST6Gal-I confers a survival advantage.

49 yposialylation), through BACE1 inhibition or ST6Gal-I constitutive overexpression, eliminates VCAM-1

50 ialic acid residues were also observed, with ST6Gal-I deficiency causing loss on endothelium and ST3G

51 Diminished immune responses due to ST6Gal-I deficiency further correlate with constitutive

52 date the mechanisms involved, we report that ST6Gal-I deficiency induces immunoglobulin M (IgM) antig

53 The EGFR inhibitor, erlotinib, neutralized ST6Gal-I-dependent differences in EGFR activation, mesen

54 ed the subcellular location and mechanism of ST6Gal I dimer formation, as well as the role of Cys res

55 ed increased dimer formation suggesting that ST6Gal I dimers may be critical in the oligomerization p

56 U937 cells with forced ST6Gal-I displayed TNFR1 with elevated alpha2-6 sialylat

57 Pulse-chase analysis demonstrated that the ST6Gal I disulfide-bonded dimer forms in the endoplasmic

58 Preventing ST6Gal-I down-regulation (and therefore integrin hyposia

59 Importantly, ST6Gal-I down-regulation results from cleavage by the BA

60 EK, but not phosphoinositide 3-kinase, block ST6Gal-I down-regulation, integrin hyposialylation, and

61 estingly, macrophage differentiation induces ST6Gal-I down-regulation, leading to reduced alpha2-6 si

62 inhibits galectin-1 death, we expressed the ST6Gal I enzyme in a galectin-1-sensitive murine T cell

63 SAalpha2,6Gal sequences, created by the ST6Gal I enzyme, are present on medullary thymocytes res

64 e for the first time the in vivo role of the ST6Gal-I enzyme in the growth and differentiation of spo

65 spondingly, at these later time points, high ST6Gal-I expressers displayed sustained activation of th

66 atient-derived xenograft tumors enriched for ST6Gal-I-expressing cells relative to pair-matched untre

67 rarely expressed ST6Gal-I, but the number of ST6Gal-I-expressing epithelial cells increased significa

68 ST6Gal I expression abrogated the reduction in CD45 tyro

69 ST6Gal I expression reduced galectin-1 binding to the ce

70 cells following viral infection, suggesting ST6Gal I expression remains high on activated B cells in

71 We demonstrate that the loss of ST6Gal I expression results in similar influenza infecti

72 Cells with high ST6Gal-I expression displayed enrichment in mesenchymal

73 These findings implicate up-regulated ST6Gal-I expression in blocking homeostatic epithelial c

74 Modulating ST6Gal-I expression in pancreatic and ovarian cancer cel

75 tive enrichment in clonal variants with high ST6Gal-I expression is observed upon prolonged serum dep

76 these results, serum-starved cells with high ST6Gal-I expression maintain a greater number of S phase

77 Similarly, ST6Gal-I expression was restricted to basal epidermal la

78 Blockade of ST6Gal-I expression with short interfering RNA reversed

79 PDAC cells, we found that knockdown (KD) of ST6Gal-I expression, as well as removal of surface alpha

80 tive enrichment of clonal variants with high ST6Gal-I expression, further substantiating a role for S

81 ls exhibited a corresponding upregulation of ST6Gal-I expression.

82 ST6Gal-I expressors (with alpha2-6 sialylated beta1 inte

83 Removal of alpha2-6 sialic acids from ST6Gal-I expressors by neuraminidase treatment restores

84 Finally, we show that beta1 integrins from ST6Gal-I expressors have increased association with tali

85 tal SW48 colonocytes (unsialylated), whereas ST6Gal-I expressors were protected.

86 er number of S phase cells compared with low ST6Gal-I expressors, reflecting enhanced proliferation.

87 However, mechanisms by which ST6Gal-I facilitates tumor progression remain poorly und

88 Galbeta1-4GlcNAc:alpha2-6-sialyltransferase (ST6Gal I); formerly ST6N).

89 sferase of protein Asn-linked glycosylation (ST6Gal I) forms disulfide-bonded dimers that exhibit dec

90 HO-K1 cells indicated that expression of the ST6Gal I gene causes selective 9-O-acetylation of alpha2

91 Thus, manipulating ST6Gal I gene expression may have therapeutic potential

92 D22 and ST6Gal-I knockout mice revealed that ST6Gal-I-generated B cell CD22L plays a role in splenic

93 c and BM-derived DCs, which does not contain ST6Gal-I-generated sialic acids and which, unlike the B

94 e oligomerization process involved in stable ST6Gal I Golgi localization.

95 sm is not the predominant mechanism used for ST6Gal I Golgi localization.

96 Although the recombinant soluble form of ST6Gal I has six cysteines, quantitative analysis indica

97 ST6Gal-I-high cells had greater a2-6 sialylation and act

98 ST6Gal-I-high cells had greater alpha2-6 sialylation and

99 rs (E-cadherin, occludin) were suppressed in ST6Gal-I-high cells.

100 enon is reproducible by stable expression of ST6Gal I in parental CHO cells, but not upon transfectio

101 beta1-integrin function, we stably expressed ST6Gal-I in a colon epithelial cell line lacking endogen

102 xpression, further substantiating a role for ST6Gal-I in cell survival.

103 hairpin RNA (shRNA)-mediated attenuation of ST6Gal-I in colon carcinoma cells with elevated endogeno

104 romoting function by highlighting a role for ST6Gal-I in EMT, which may be mediated, at least in part

105 romoting function by highlighting a role for ST6Gal-I in EMT, which may be mediated, at least in part

106 hese results implicate a functional role for ST6Gal-I in fostering tumor cell survival within the ser

107 al Suit2 cells, and forced overexpression of ST6Gal-I in the Suit2 line was sufficient to activate EM

108 This first in vivo evidence for a role of ST6Gal-I in tumor progression was confirmed using a nove

109 ubset development, whereas the DC-associated ST6Gal-I-independent CD22L may be required for the maint

110 sfection of CHO-GD3-OAc(-) mutant cells with ST6Gal-I induced 9-O-acetylation specifically on sialyla

111 Finally, we found that ST6Gal-I induced expression of the key tumor-promoting t

112 The ST6Gal I is a sialyltransferase that functions in the la

113 The ST6Gal I is expressed as two isoforms with a single amin

114 that increased epithelial cell expression of ST6Gal-I is associated with premalignant progression.

115 c cells and primary human CD14(+) monocytes, ST6Gal-I is down-regulated, leading to beta1 hyposialyla

116 ST6Gal-I is itself a glycoprotein, and in this initial a

117 The glycosyltransferase ST6Gal-I is known to block homeostatic apoptosis through

118 Here we show that ST6Gal-I is upregulated in ovarian and pancreatic carcin

119 The alpha-2,6-sialyltransferase (ST6Gal-I) is a key enzyme that regulates the distributio

120 the stable or transient localization of the ST6Gal I isoforms in the Golgi.

121 These two ST6Gal I isoforms were used to explore the role of the b

122 We have found that the ST6Gal-I isoforms are phosphorylated on luminal Ser and

123 ST6Gal-I KD also alters mRNA expression of key gemcitabi

124 ST6Gal-I KD in S2-013 cells increases gemcitabine-mediat

125 Using ST6Gal-I knockdown and forced overexpression colon carci

126 ing pancreatic and ovarian cancer cells with ST6Gal-I knockdown or overexpression, we determined that

127 ubcutaneous tumor formation was inhibited by ST6Gal-I knockdown, whereas in a chemically induced tumo

128 as S2-013 and S2-LM7AA cells with or without ST6Gal-I knockdown.

129 of splenic and BM B cell subsets in CD22 and ST6Gal-I knockout mice revealed that ST6Gal-I-generated

130 isoforms of the alpha2,6-sialyltransferase (ST6Gal I) leads to differences in their trafficking, pro

131 , we find that serum-starved cells with high ST6Gal-I levels exhibit increased activation of prosurvi

132 nded TNF treatment (6-24 h), cells with high ST6Gal-I levels exhibited resistance to TNF-induced apop

133 ine-resistant MiaPaCa-2 cells display higher ST6Gal-I levels than treatment-naive cells along with a

134 In normal colon, ST6Gal-I localized selectively to the base of crypts, wh

135 ronectin) and cell invasiveness, relative to ST6Gal-I-low cells.

136 a2-6 sialylation and activation of EGFR than ST6Gal-I-low cells.

137 a2-6 sialylation and activation of EGFR than ST6Gal-I-low cells.

138 metastasis and poor survival, and therefore ST6Gal-I-mediated hypersialylation likely plays a role i

139 transfer purified B cells from wild-type or ST6Gal I(-/-) mice into B cell-deficient (microMT(-/-))

140 At later memory time points, ST6Gal I(-/-) mice show comparable numbers of IgG influe

141 ntiviral B cell immune response, we infected ST6Gal I(-/-) mice with influenza A/HKx31.

142 ST6Gal-I mRNA has been reported to be upregulated in hum

143 versed collagen binding back to the level of ST6Gal-I nonexpressors, confirming that alpha2-6 sialyla

144 Tissues of ST6Gal-I null mice showed minimal binding of an alpha2-6

145 Up-regulation of ST6Gal-I occurs in many cancers, including colon carcino

146 Here, we investigated the impact of ST6Gal-I on cell mechanics.

147 ith TRAIL, implicating a selective effect of ST6Gal-I on the Fas receptor.

148 g that O-acetylation is not induced when the ST6Gal I or ST8Sia I cDNAs are overexpressed in SV40 T a

149 erentially accepted by the sialyltransferase ST6Gal-I over ST3Gal-IV, leading to the favored incorpor

150 umor initiation model, mice with conditional ST6Gal-I overexpression exhibited enhanced tumorigenesis

151 d on ST6Gal-I overexpression, because forced ST6Gal-I overexpression in normal gastric stem cell-diff

152 arian and pancreatic cancer cell models with ST6Gal-I overexpression or knockdown, we find that serum

153 ature of EMT) in Suit2 cells with or without ST6Gal-I overexpression, as well as S2-013 and S2-LM7AA

154 ction from TNF-induced apoptosis depended on ST6Gal-I overexpression, because forced ST6Gal-I overexp

155 This suggests that the bulk of the ST6Gal-I phosphorylation is occurring in the Golgi.

156 Elevated ST6Gal-I positively correlates with metastasis and poor

157 Additionally, KD of ST6Gal-I potentiates gemcitabine-induced DNA damage as m

158 Because the ST6Gal I preferentially utilizes N-glycans as acceptor s

159 In addition, the sialyltransferase ST6Gal-I promotes epidermal growth factor receptor (EGFR

160 Collectively, our results suggest that ST6Gal-I promotes tumorigenesis and may serve as a regul

161 Here, we show upregulated ST6Gal-I protein in several epithelial cancers, includin

162 s has limited immunochemical analysis of the ST6Gal-I protein.

163 , S2-LM7AA, and S2-013, exhibit up-regulated ST6Gal-I relative to parental Suit2 cells.

164 Protein glycosylation by ST6Gal-I restricts access of antigen receptors and Shp-1

165 To gain mechanistic insight into ST6Gal-I's role in EMT, we examined the activity of epid

166 In this study, we investigated ST6Gal-I's role in epithelial to mesenchymal transition

167 , these results advance our understanding of ST6Gal-I's tumor-promoting function by highlighting a ro

168 , these results advance our understanding of ST6Gal-I's tumor-promoting function by highlighting a ro

169 BACE1 up-regulation, ST6Gal-I shedding, beta1 hyposialylation, and alpha4beta

170 th suppressed BCR signaling, B cells lacking ST6Gal I showed a net redistribution of the BCR to clath

171 her neuraminidase treatment or expression of ST6Gal-I shRNA markedly enhanced TNFalpha-mediated apopt

172 ged by exogenously administering recombinant ST6Gal I sialyltransferase and azide-modified CMP-Neu5Ac

173 duces a down-regulation in expression of the ST6Gal I sialyltransferase.

174 The ST6Gal-I sialyltransferase adds an alpha2-6-linked siali

175 Here, we report a novel role for the ST6Gal-I sialyltransferase in gemcitabine resistance.

176 The ST6Gal-I sialyltransferase produces Siglec ligands for t

177 onocyte/macrophage lineage down-regulate the ST6Gal-I sialyltransferase via a protein kinase C/Ras/ER

178 In this study, we report that the ST6Gal-I sialyltransferase, an enzyme up-regulated in nu

179 ds, a carbohydrate modification added by the ST6Gal-I sialyltransferase.

180 ion of the CD22 glycan ligand(s) produced by ST6Gal-I sialyltransferase.

181 alylation of the TNFR1 death receptor by the ST6Gal-I sialyltransferase.

182 a-galactoside alpha-2,6-sialyltransferase 1 (ST6Gal-I) sialyltransferase, which is up-regulated in nu

183 Although both ST3Gal-IV and ST6Gal-I sialyltransferases mask galactose linkages impl

184 Expression of the ST6Gal I specifically resulted in increased sialylation

185 entify the death receptor, Fas (CD95), as an ST6Gal-I substrate, and show that alpha2-6 sialylation o

186 ric epithelial stem cells strongly expressed ST6Gal-I, suggesting a novel biomarker of stemness.

187 gainst beta1, beta3, and beta5 integrins and ST6Gal-I targets EGFR, tumor necrosis factor receptor, a

188 B cells deficient in the enzyme (ST6Gal I) that forms the CD22 ligand show suppressed BCR

189 as-dependent alteration in the expression of ST6Gal I, the enzyme that adds alpha2-6-linked sialic ac

190 pha2-6 sialylation and increased activity of ST6Gal-I, the Golgi glycosyltransferase that creates alp

191 that that uses alpha-2,6-sialyltransferase (ST6Gal-I) to enzymatically add 13C-N-acetylneuraminic ac

192 Furthermore, the ST6Gal I transfectants produced no intracranial tumors i

193 Galbeta1,4GlcNAc alpha2,6-sialyltransferase (ST6Gal I) transfectants were made to replace the endogen

194 d vector-transfected control cells in vitro, ST6Gal I transfection abolished invasion in vitro and in

195 mice in comparison with animals deficient in ST6Gal-I (transfers alpha2-6-linked sialic acid to Galbe

196 FR1 sialylation, we generated overexpressing ST6Gal-I transgenic mice.

197 Notably, ST6Gal-I upregulation in cancer cells conferred hallmark

198 r previous study the larger L-sialylmotif of ST6Gal I was analyzed by site-directed mutagenesis, whic

199 The catalytic domain from rat ST6Gal-I was expressed in mammalian HEK293 cells.

200 ST6Gal-I was highly expressed in induced pluripotent ste

201 sion due to the various 13C-NeuAc adducts on ST6Gal-I was observed in a 3D experiment correlating 1H-

202 determine the functional impact of increased ST6Gal-I, we generated human gastric antral organoids fr

203 uced by the human alpha2-6 sialyltransferase ST6Gal-I, were identified as potent anti-inflammatory me

204 The glycosyltransferase ST6Gal-I, which adds alpha2-6-linked sialic acids to sub

205 ialyltransferases ST3Gal-III, ST3Gal-IV, and ST6Gal-I, which together are responsible for addition of

206 s, we investigated further an association of ST6Gal-I with cancer stem cells (CSC).

207 ed removal of the native NeuAc residues from ST6Gal-I with neuraminidase, separation of the neuramind