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SHC1 sensitizes cancer cells to the 8-Cl-cAMP treatment

Title
SHC1 sensitizes cancer cells to the 8-Cl-cAMP treatment
Authors
Choi, Ki YoungCho, Young JunKim, Jeong SeonAhn, Young-HoHong, Seung Hwan
Ewha Authors
안영호
SCOPUS Author ID
안영호scopus
Issue Date
2015
Journal Title
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
ISSN
0006-291XJCR Link

1090-2104JCR Link
Citation
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS vol. 463, no. 4, pp. 673 - 678
Keywords
8-Chloro-cyclic AMPSHC1AMP-activated protein kinasep38 MAP kinaseCancer therapy
Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
Indexed
SCI; SCIE; SCOPUS WOS scopus
Document Type
Article
Abstract
8-Chloro-cyclic AMP (8-Cl-cAMP) is a cyclic AMP analog that induces growth inhibition and apoptosis in a broad spectrum of cancer cells. Previously, we found that 8-Cl-cAMP-induced growth inhibition is mediated by AMP-activated protein kinase (AMPK) as well as p38 mitogen-activated protein kinase (p38 MAPK). To identify downstream mediators of the 8-Cl-cAMP signaling, we performed co-immunoprecipitation combined with mass spectrometry using the anti-AMPK or p38 MAPK antibodies. Through this approach, SHC1 was identified as one of the binding partners of p38 MAPK. SHC1 phosphorylation was suppressed by 8-Cl-CAMP in HeLa and MCF7 cancer cells, which was mediated by its metabolites, 8-Cl-adenosine and 8-Cl-ATP; however, 8-Cl-cAMP showed no effect on SHC1 phosphorylation in normal human fibroblasts. SHC1 siRNA induced AMPK and p38 MAPK phosphorylation and growth inhibition in cancer cells, and SHC1 overexpression re-sensitized human foreskin fibroblasts to the 8-Cl-CAMP treatment. SHC1 phosphorylation was unaffected by Compound C (an AMPK inhibitor) and SB203580 (a p38 MAPK inhibitor), which suggests that SHC1 is upstream of AMPK and p38 MAPK in the 8-Cl-CAMP-stimulated signaling cascade. On the basis of these findings, we conclude that SHC1 functions as a sensor during the 8-Cl-cAMP-induced growth inhibition in SHC1-overexpressing cancer cells. (C) 2015 Elsevier Inc. All rights reserved.
DOI
10.1016/j.bbrc.2015.05.123
Appears in Collections:
의과대학 > 의학과 > Journal papers
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