A novel sialyltransferase inhibitor AL10 suppresses invasion and metastasis of lung cancer cells by inhibiting integrin‐mediated signaling

@article{Chiang2010ANS,
  title={A novel sialyltransferase inhibitor AL10 suppresses invasion and metastasis of lung cancer cells by inhibiting integrin‐mediated signaling},
  author={Chi-Hsiang Chiang and Chie-Hong Wang and Hui‐Chiu Chang and Shivaji V. More and Wen-Shan Li and Wen Chun Hung},
  journal={Journal of Cellular Physiology},
  year={2010},
  volume={223}
}
Aberrant sialylation catalyzed by sialyltransferases (STs) is frequently found in cancer cells and is associated with increased cancer metastasis. However, ST inhibitors developed till now are not applicable for clinical use because of their poor cell permeability. In this study, a novel ST inhibitor AL10 derived from the lead compound lithocholic acid identified in our previous study is synthesized and the anti‐cancer effect of this compound is studied. AL10 is cell‐permeable and effectively… 
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References

SHOWING 1-10 OF 40 REFERENCES
ST6Gal-I expression in ovarian cancer cells promotes an invasive phenotype by altering integrin glycosylation and function
TLDR
ST6Gal-I mediated sialylation of β1 integrins in ovarian cancer cells may contribute to peritoneal metastasis by altering tumor cell adhesion and migration through extracellular matrix.
Carbohydrate‐mediated cell adhesion in cancer metastasis and angiogenesis
TLDR
Results have confirmed that sialyl Lewisa/x determinants are not merely markers for cancers, but are functionally implicated in the malignant behavior of cancer cells, and suggested that the increase of these determinants in malignant cells is an inevitable consequence of themalignant transformation of cells.
Hypersialylation of beta1 integrins, observed in colon adenocarcinoma, may contribute to cancer progression by up-regulating cell motility.
TLDR
Findings suggest that beta1 hypersialylation may augment colon tumor progression by altering cell preference for certain extracellular matrix milieus, as well as by stimulating cell migration.
Relationship of sialyl-Lewis(x/a) underexpression and E-cadherin overexpression in the lymphovascular embolus of inflammatory breast carcinoma.
TLDR
These findings support the cooperative relationship of sLe(x/a) underexpression and E-cadherin overexpression in the genesis of the lymphovascular embolus of IBC.
Significance of Integrin α5 Gene Expression as a Prognostic Factor in Node-negative Non-Small Cell Lung Cancer
TLDR
Investigation of the expression of α5β1 integrin in 20 lung cancer cell lines and in 88 node-negative non-small cell lung cancers by RT-PCR and immunohistochemical assays found that the integrin α5 expression was significantly associated with the status of differentiation and the age of the patients.
Ras oncogene directs expression of a differentially sialylated, functionally altered β1 integrin
TLDR
Using a cell-free receptor/ligand-binding assay, it is shown that purified, desialylated α1β1 integrins have diminished collagen-binding capability, providing strong evidence that sialic acids play a causal role in regulating β1 integrin function.
alpha 2-6-Linked sialic acids on N-glycans modulate carcinoma differentiation in vivo.
TLDR
First in vivo evidence for a role of ST6Gal-I in tumor progression was confirmed using a novel approach, which conditionally restored St6gal1 in cell lines derived from the null tumors.
CYR61 and alphaVbeta5 integrin cooperate to promote invasion and metastasis of tumors growing in preirradiated stroma.
TLDR
It is shown that tumor cells derived from SCCVII and HCT116 tumors growing in a preirradiated bed, or selected in vitro through repeated cycles of severe hypoxia, retain invasive and metastatic capacities when returned to normoxia.
The Kazal motifs of RECK protein inhibit MMP-9 secretion and activity and reduce metastasis of lung cancer cells in vitro and in vivo
TLDR
The results suggest that the K23 motifs of RECK protein can inhibit MMP‐9 secretion and activity and attenuate metastasis of lung cancer cells.
Immunohistochemical expression of integrins and extracellular matrix proteins in non-small cell lung cancer: correlation with lymph node metastasis.
TLDR
Increased expression of integrins alpha5 and beta1, and lost expression of collagen matrices significantly correlated with LN metastasis of NSCLC might promote tumor cell survival and invasiveness.
...
1
2
3
4
...