In:
Cancer Science, Wiley, Vol. 109, No. 1 ( 2018-01), p. 141-153
Abstract:
Ganglioside GD 2 is specifically expressed in small‐cell lung cancer ( SCLC ) cells, leading to enhancement of malignant phenotypes, such as cell proliferation and migration. However, how GD 2 promotes malignant phenotypes in SCLC cells is not well known. In this study, to reveal the mechanisms by which GD 2 increases malignant phenotypes in SCLC cells, we used enzyme‐mediated activation of radical sources combined with mass spectrometry in GD 2 + SCLC cells. Consequently, we identified ASC amino acid transporter 2 ( ASCT 2), a major glutamine transporter, which coordinately works with GD 2. We showed that ASCT 2 was highly expressed in glycolipid‐enriched microdomain/rafts in GD 2 + SCLC cells, and colocalized with GD 2 in both proximity ligation assay and immunocytostaining, and bound with GD 2 in immunoprecipitation/ TLC immunostaining. Malignant phenotypes of GD 2 + SCLC cells were enhanced by glutamine uptake, and were suppressed by L‐γ‐glutamyl‐p‐nitroanilide, a specific inhibitor of ASCT 2, through reduced phosphorylation of p70 S6K1 and S6. These results suggested that ASCT 2 enhances glutamine uptake in glycolipid‐enriched microdomain/rafts in GD 2 + SCLC cells, leading to the enhancement of cell proliferation and migration through increased phosphorylation of the mTOR complex 1 signaling axis.
Type of Medium:
Online Resource
ISSN:
1347-9032
,
1349-7006
DOI:
10.1111/cas.2018.109.issue-1
Language:
English
Publisher:
Wiley
Publication Date:
2018
detail.hit.zdb_id:
2115647-5
detail.hit.zdb_id:
2111204-6
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